TY  - JOUR
AU  - Janić, Dragana
AU  - Perić, Jelena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Stanić, Bojana
AU  - Pejanović, Nadja
AU  - Dokmanović, Lidija
AU  - Lazić, Jelena
AU  - Krstovski, Nada
AU  - Virijević, Marijana
AU  - Tomin, Dragica
AU  - Vidović, Ana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1303
AB  - lt b gt Uvod: lt /b gt  Akutna limfoblastna leukemija (ALL) je najčešće maligno oboljenje kod dece, dok je kod odraslih njena učestalost mnogo niža. U današnjoj kliničkoj praksi kao najvažnije metode stratifikacije pacijenata u određene grupe rizika koriste se metode identifikacije citogenetičkih aberacija i malog broja molekulanih markera. Tehnologija sekvenciranja nove generacije (SNG) obezbeđuje veliku količinu podataka koji doprinose razjašnjavanju mutacionog profila dečje (dALL) i adultne ALL (aALL).  lt b gt Metode: lt /b gt  Uzorci DNK iz 34 dALL i aALL pacijenata analizirani su primenom SNG ciljanog sekvenciranja ("TruSeq Amplicon Cancer Panel - TSACP") kojim se sekvenciraju "hotspot" mutacije u 48 gena povezanih sa kancerom.  lt b gt Rezultati: lt /b gt  Identifikovano je ukupno 330 varijanti u kodirajućim regionima, od kojih je samo 95 njih za posledicu imalo potencijalnu promenu u proteinu. Posmatrano kod pojedinačnih pacijenata, detektovane mutacije su pretežno remetile Ras/RTK signalni put (STK11, KIT, MET, NRAS, KRAS, PTEN). Pored toga, identifikovano je 5 pacijenata sa istom mutacijom u HNF1A genu, koja je uzrokovala poremećaje u Wnt i Notch signalnom putu. Kod dva pa cijenta otkrivene su varijante u NOTCH1 genu. Nije detektovano istovremeno prisustvo varijanti u HNF1A i NOTCH1 genu, dok su geni uključeni u Ras/RTK signalni put pokazali tendenciju ka akumuliranju mutacija.  lt b gt Zaključak: lt /b gt  Naši rezultati pokazuju da ALL sadrži Mali broj mutacija, bez značajnih razlika između dALL i aALL (medijana po pacijentu 2 odnosno 3). Detektovane mutacije izazivaju poremećaje u nekoliko ključnih signalnih puteva, prvenstveno Ras/RTK kaskade. Ova studija doprinosi ukupnom znanju o mutacionom profilu ALL, što vodi ka boljem razumijevanju molekularne osnove ovog oboljenja.
AB  - lt b gt Background: lt /b gt  Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL).  lt b gt Methods: lt /b gt  We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes.  lt b gt Results: lt /b gt  We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation.  lt b gt Conclusions: lt /b gt  Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom
T1  - Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia
EP  - 82
IS  - 1
SP  - 72
VL  - 39
DO  - 10.2478/jomb-2019-0017
ER  - 

@article{
author = "Janić, Dragana and Perić, Jelena and Karan-Đurašević, Teodora and Kostić, Tatjana and Marjanović, Irena and Stanić, Bojana and Pejanović, Nadja and Dokmanović, Lidija and Lazić, Jelena and Krstovski, Nada and Virijević, Marijana and Tomin, Dragica and Vidović, Ana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "lt b gt Uvod: lt /b gt  Akutna limfoblastna leukemija (ALL) je najčešće maligno oboljenje kod dece, dok je kod odraslih njena učestalost mnogo niža. U današnjoj kliničkoj praksi kao najvažnije metode stratifikacije pacijenata u određene grupe rizika koriste se metode identifikacije citogenetičkih aberacija i malog broja molekulanih markera. Tehnologija sekvenciranja nove generacije (SNG) obezbeđuje veliku količinu podataka koji doprinose razjašnjavanju mutacionog profila dečje (dALL) i adultne ALL (aALL).  lt b gt Metode: lt /b gt  Uzorci DNK iz 34 dALL i aALL pacijenata analizirani su primenom SNG ciljanog sekvenciranja ("TruSeq Amplicon Cancer Panel - TSACP") kojim se sekvenciraju "hotspot" mutacije u 48 gena povezanih sa kancerom.  lt b gt Rezultati: lt /b gt  Identifikovano je ukupno 330 varijanti u kodirajućim regionima, od kojih je samo 95 njih za posledicu imalo potencijalnu promenu u proteinu. Posmatrano kod pojedinačnih pacijenata, detektovane mutacije su pretežno remetile Ras/RTK signalni put (STK11, KIT, MET, NRAS, KRAS, PTEN). Pored toga, identifikovano je 5 pacijenata sa istom mutacijom u HNF1A genu, koja je uzrokovala poremećaje u Wnt i Notch signalnom putu. Kod dva pa cijenta otkrivene su varijante u NOTCH1 genu. Nije detektovano istovremeno prisustvo varijanti u HNF1A i NOTCH1 genu, dok su geni uključeni u Ras/RTK signalni put pokazali tendenciju ka akumuliranju mutacija.  lt b gt Zaključak: lt /b gt  Naši rezultati pokazuju da ALL sadrži Mali broj mutacija, bez značajnih razlika između dALL i aALL (medijana po pacijentu 2 odnosno 3). Detektovane mutacije izazivaju poremećaje u nekoliko ključnih signalnih puteva, prvenstveno Ras/RTK kaskade. Ova studija doprinosi ukupnom znanju o mutacionom profilu ALL, što vodi ka boljem razumijevanju molekularne osnove ovog oboljenja., lt b gt Background: lt /b gt  Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL).  lt b gt Methods: lt /b gt  We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes.  lt b gt Results: lt /b gt  We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation.  lt b gt Conclusions: lt /b gt  Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom, Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia",
pages = "82-72",
number = "1",
volume = "39",
doi = "10.2478/jomb-2019-0017"
}

Janić, D., Perić, J., Karan-Đurašević, T., Kostić, T., Marjanović, I., Stanić, B., Pejanović, N., Dokmanović, L., Lazić, J., Krstovski, N., Virijević, M., Tomin, D., Vidović, A., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 39(1), 72-82.
https://doi.org/10.2478/jomb-2019-0017

Janić D, Perić J, Karan-Đurašević T, Kostić T, Marjanović I, Stanić B, Pejanović N, Dokmanović L, Lazić J, Krstovski N, Virijević M, Tomin D, Vidović A, Suvajdžić-Vuković N, Pavlović S, Tošić N. Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom. in Journal of Medical Biochemistry. 2020;39(1):72-82.
doi:10.2478/jomb-2019-0017 .

Janić, Dragana, Perić, Jelena, Karan-Đurašević, Teodora, Kostić, Tatjana, Marjanović, Irena, Stanić, Bojana, Pejanović, Nadja, Dokmanović, Lidija, Lazić, Jelena, Krstovski, Nada, Virijević, Marijana, Tomin, Dragica, Vidović, Ana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom" in Journal of Medical Biochemistry, 39, no. 1 (2020):72-82,
https://doi.org/10.2478/jomb-2019-0017 . .

TY  - JOUR
AU  - Sarajlija, Adrijan
AU  - Đorđević, Maja
AU  - Kecman, Bozica
AU  - Skakić, Anita
AU  - Pavlović, Sonja
AU  - Pasić, Srdjan
AU  - Stojiljković, Maja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1387
AB  - Background: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. Methods: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. Results: Absolute neutrophil count (ANC)  lt  1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC  lt  500/mm(3)) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T  gt  A/c.785G  gt  A and c.81T  gt  A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G  gt  A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. Conclusions: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI.
PB  - Elsevier, Amsterdam
T2  - European Journal of Medical Genetics
T1  - Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib
IS  - 3
VL  - 63
DO  - 10.1016/j.ejmg.2019.103767
ER  - 

@article{
author = "Sarajlija, Adrijan and Đorđević, Maja and Kecman, Bozica and Skakić, Anita and Pavlović, Sonja and Pasić, Srdjan and Stojiljković, Maja",
year = "2020",
abstract = "Background: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. Methods: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. Results: Absolute neutrophil count (ANC)  lt  1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC  lt  500/mm(3)) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T  gt  A/c.785G  gt  A and c.81T  gt  A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G  gt  A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. Conclusions: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI.",
publisher = "Elsevier, Amsterdam",
journal = "European Journal of Medical Genetics",
title = "Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib",
number = "3",
volume = "63",
doi = "10.1016/j.ejmg.2019.103767"
}

Sarajlija, A., Đorđević, M., Kecman, B., Skakić, A., Pavlović, S., Pasić, S.,& Stojiljković, M.. (2020). Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib. in European Journal of Medical Genetics
Elsevier, Amsterdam., 63(3).
https://doi.org/10.1016/j.ejmg.2019.103767

Sarajlija A, Đorđević M, Kecman B, Skakić A, Pavlović S, Pasić S, Stojiljković M. Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib. in European Journal of Medical Genetics. 2020;63(3).
doi:10.1016/j.ejmg.2019.103767 .

Sarajlija, Adrijan, Đorđević, Maja, Kecman, Bozica, Skakić, Anita, Pavlović, Sonja, Pasić, Srdjan, Stojiljković, Maja, "Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib" in European Journal of Medical Genetics, 63, no. 3 (2020),
https://doi.org/10.1016/j.ejmg.2019.103767 . .

TY  - THES
AU  - Anđelković, Marina
PY  - 2019
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7976
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:23341/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025217970
UR  - https://nardus.mpn.gov.rs/handle/123456789/18067
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/54
AB  - Primarna cilijarna diskinezija (PCD) predstavlja retku bolest koja se nasleđuje na autozomno recesivan način ili je nasleđivanje vezano za hromozom X, i predominantno utiče na funkcionisanje pluća, reproduktivnih organa i na lateralnost unutrašnjih organa. PCD je klinički i genetički veoma heterogen poremećaj koji se javlja odmah po rođenju, a karakteriše se promenama na motornim cilijama koje su posledica patogenih varijanti u genima koji kodiraju za proteine koji su neophodni za pravilnu strukturu i funkciju ovih organela. Do sada je opisano 38 gena uzročnika bolesti koje su odgovorne za nastanak PCD-a, a smatra se da je taj broj mnogo veći s obzirom da 2500 proteina učestvuje u izgradnji i pravilnom funkcionisanju cilija. Velika raznolikost kliničke slike PCD pacijenata često dovodi do odloženog uspostavljanja precizne dijagnoze ove bolesti, a nije retkost i da pacijenti sa drugim bolestima pluća budu okarakterisani kao PCD pacijenti. Genetički profil ove bolesti kod pacijenata sa teritorije Srbije do sada nije utvrđen, pa je identifikacija gena uzročnika neophodna. Stoga je u okviru ove teze urađeno genomsko profilisanje pacijenata sa primarnom cilijarnom diskinezijom u cilju razvoja genetičkog algoritma koji bi, osim opisanih patogenih genetičkih varijanti i gena uzročnika, obuhvatio i novootkrivene varijante u kodirajućim regionima gena uzročnika PCD-a i gena kandidata za PCD. Sve ovo omogućava razvoj strategije za diferencijalnu dijagnozu PCD-a i drugih bolesti pluća suspektnih na ciliopatije koji se klinički manifestuju kao PCD. Takođe, pristupljeno je funkcionalnoj karakterizaciji novootkrivenih patogenih varijanti u već poznatim genima koji su odgovorni za razvoj PCD-a i/ili u genima koji do sada nisu asocirani sa PCD-om, a koji bi mogli da dovedu do karakterističnog fenotipa kod pacijenta. Jedna od glavnih odlika PCD pacijenata je strukturna i/ili funkcionalna promena na cilijama, pa su one nepokretne, slabo pokretne, promenjen im je obrazac kretanja ili odsustvuju...
AB  - Primary ciliary dyskinesia (PCD) is a rare disease that is inherited in autosomal recessive manner or the inheritance is X-linked, and predominantly affects the functioning of the lungs, reproductive organs and the laterality of the internal organs. PCD is clinically and genetically very heterogeneous disorder that occurs immediately after birth, and is characterized by alterations in motor cilia due to pathogenic variants in genes encoding proteins that are necessary for the proper structure and function of these organelles. So far, there have been described 38 PCD-causative genes, and this number is considered to be much higher given that 2500 proteins participate in the formation and functioning of the cilia. Clinical heterogeneity of PCD patients often leads to the delayed establishment of a precise diagnosis of the disease, and it is not unusual that patients with other lung diseases are classified as PCD patients. The genetic background of the disease in patients with Serbian descent has not been established so far, so the mutational profile involved in the pathogenesis of PCD is necessary. Therefore, within this thesis, genomic profiling of patients with primary ciliary dyskinesia was performed in order to develop a genetic algorithm that, in addition to the described disease-causing pathogenic genetic variants and genes, would include novel variants in the coding regions of PCD-causative and candidate genes. This approach allows the establishment of a strategy for the differential diagnosis of PCD and other lung diseases suspected to ciliopathies that are clinically manifested as PCD. Functional characterization of a novel potentially pathogenic variant in PCD disease-causing genes and genes that have not been associated with PCD so far, but could be associated with the characteristic phenotype of PCD, was performed. One of the main features of PCD is ultrastructural defects of cilia leading to ciliary immotility, abnormal motility, or their absence...
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Genomski profil pacijenata dečijeg uzrasta sa primarnom cilijarnom diskinezijom: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih genetičkih varijanti
T1  - Genomic profiling of pediatric patients with primary ciliary dyskinesia: genotype-phenotype correlation and functional characterization of novel genetic variants
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18067
ER  - 

@phdthesis{
author = "Anđelković, Marina",
year = "2019",
abstract = "Primarna cilijarna diskinezija (PCD) predstavlja retku bolest koja se nasleđuje na autozomno recesivan način ili je nasleđivanje vezano za hromozom X, i predominantno utiče na funkcionisanje pluća, reproduktivnih organa i na lateralnost unutrašnjih organa. PCD je klinički i genetički veoma heterogen poremećaj koji se javlja odmah po rođenju, a karakteriše se promenama na motornim cilijama koje su posledica patogenih varijanti u genima koji kodiraju za proteine koji su neophodni za pravilnu strukturu i funkciju ovih organela. Do sada je opisano 38 gena uzročnika bolesti koje su odgovorne za nastanak PCD-a, a smatra se da je taj broj mnogo veći s obzirom da 2500 proteina učestvuje u izgradnji i pravilnom funkcionisanju cilija. Velika raznolikost kliničke slike PCD pacijenata često dovodi do odloženog uspostavljanja precizne dijagnoze ove bolesti, a nije retkost i da pacijenti sa drugim bolestima pluća budu okarakterisani kao PCD pacijenti. Genetički profil ove bolesti kod pacijenata sa teritorije Srbije do sada nije utvrđen, pa je identifikacija gena uzročnika neophodna. Stoga je u okviru ove teze urađeno genomsko profilisanje pacijenata sa primarnom cilijarnom diskinezijom u cilju razvoja genetičkog algoritma koji bi, osim opisanih patogenih genetičkih varijanti i gena uzročnika, obuhvatio i novootkrivene varijante u kodirajućim regionima gena uzročnika PCD-a i gena kandidata za PCD. Sve ovo omogućava razvoj strategije za diferencijalnu dijagnozu PCD-a i drugih bolesti pluća suspektnih na ciliopatije koji se klinički manifestuju kao PCD. Takođe, pristupljeno je funkcionalnoj karakterizaciji novootkrivenih patogenih varijanti u već poznatim genima koji su odgovorni za razvoj PCD-a i/ili u genima koji do sada nisu asocirani sa PCD-om, a koji bi mogli da dovedu do karakterističnog fenotipa kod pacijenta. Jedna od glavnih odlika PCD pacijenata je strukturna i/ili funkcionalna promena na cilijama, pa su one nepokretne, slabo pokretne, promenjen im je obrazac kretanja ili odsustvuju..., Primary ciliary dyskinesia (PCD) is a rare disease that is inherited in autosomal recessive manner or the inheritance is X-linked, and predominantly affects the functioning of the lungs, reproductive organs and the laterality of the internal organs. PCD is clinically and genetically very heterogeneous disorder that occurs immediately after birth, and is characterized by alterations in motor cilia due to pathogenic variants in genes encoding proteins that are necessary for the proper structure and function of these organelles. So far, there have been described 38 PCD-causative genes, and this number is considered to be much higher given that 2500 proteins participate in the formation and functioning of the cilia. Clinical heterogeneity of PCD patients often leads to the delayed establishment of a precise diagnosis of the disease, and it is not unusual that patients with other lung diseases are classified as PCD patients. The genetic background of the disease in patients with Serbian descent has not been established so far, so the mutational profile involved in the pathogenesis of PCD is necessary. Therefore, within this thesis, genomic profiling of patients with primary ciliary dyskinesia was performed in order to develop a genetic algorithm that, in addition to the described disease-causing pathogenic genetic variants and genes, would include novel variants in the coding regions of PCD-causative and candidate genes. This approach allows the establishment of a strategy for the differential diagnosis of PCD and other lung diseases suspected to ciliopathies that are clinically manifested as PCD. Functional characterization of a novel potentially pathogenic variant in PCD disease-causing genes and genes that have not been associated with PCD so far, but could be associated with the characteristic phenotype of PCD, was performed. One of the main features of PCD is ultrastructural defects of cilia leading to ciliary immotility, abnormal motility, or their absence...",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Genomski profil pacijenata dečijeg uzrasta sa primarnom cilijarnom diskinezijom: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih genetičkih varijanti, Genomic profiling of pediatric patients with primary ciliary dyskinesia: genotype-phenotype correlation and functional characterization of novel genetic variants",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18067"
}

Anđelković, M.. (2019). Genomski profil pacijenata dečijeg uzrasta sa primarnom cilijarnom diskinezijom: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih genetičkih varijanti. 
Univerzitet u Beogradu, Biološki fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_18067

Anđelković M. Genomski profil pacijenata dečijeg uzrasta sa primarnom cilijarnom diskinezijom: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih genetičkih varijanti. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_18067 .

Anđelković, Marina, "Genomski profil pacijenata dečijeg uzrasta sa primarnom cilijarnom diskinezijom: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih genetičkih varijanti" (2019),
https://hdl.handle.net/21.15107/rcub_nardus_18067 .

TY  - THES
AU  - Gašić, Vladimir
PY  - 2019
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=6926
UR  - https://nardus.mpn.gov.rs/handle/123456789/11509
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:20286/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025219506
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/55
AB  - Personalizovana medicina, medicina XXI veka, nastoji da individualizuje terapiju za svakog pacijenta, kako bi lečenje bilo što efikasnije i sa što manje rizika od toksičnosti. Personalizovana medicina se danas najviše oslanja na farmakogenomiku i farmakotranskriptomiku, koje su već dale svoj doprinos unapređenju lečenja mnogih bolesti, a posebno maligniteta. Akutna limfoblastna leukemija (ALL) predstavlja najčešći hematološki malignitet pedijatrijskog uzrasta. Mada stopa izlečenja dostiže 80-90%, ALL je i dalje glavni uzrok mortaliteta u ovih pacijenata. Terapija izaziva neželjene efekte u 75% pacijenata. Pored toga, u 1-3% pedijatrijskih pacijenata sa ALL smrtni ishod nije posledica bolesti, već je uzrokovan terapijom. Lečenje pedijatrijske ALL nije napredovalo uvođenjem novih lekova, već nastojanjem da se smanje neželjena dejstva onih lekova koji su već sastavni delovi postojećih terapijskih protokola, zbog čega su farmakogenomika i farmakotranskriptomika dobile ključno mesto u ovoj oblasti. Glukokortikoidni lekovi (GK) se koriste u početnoj fazi lečenja ALL u dece, u fazi indukcije remisije. Od početka lečenja do 8. dana se primenjuju isključivo GK. Ipak, farmakogenomske i farmakotranskriptomske studije za glukokortikoidne lekove još uvek nisu dovele do algoritma koji bi mogao biti primenjen u lečenju dečje ALL. Stoga je izuzetno značajno nastaviti sa istraživanjima farmakogenomskih i farmakotranskriptomskih markera relevantnih za uspešnost GK terapije u dece sa ALL. Razumevanje molekularnog mehanizma dejstva GK vodi ka otkrivanju novih markera koji mogu biti iskorišćeni za optimizaciju GK terapije. Nove tehnologije, kao što je sekvenciranje nove generacije (eng, next generation sequencing, NGS) su omogućile dizajniranje panela za farmakogenomske i farmakotranskriptomske markere za različite lekove...
AB  - Personalized medicine, the medicine of the XXI century, aims to individualize therapy for each patient, in order for the treatment to be as efficient and safe as possible. Today, personalized medicine is the most reliant on pharmacogenomics and pharmacotranscriptomics, which have already given their contribution to enhancing treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy of childhood. Even though the percentage of cured patients reaches 80-90%, ALL is still the main cause of mortality in this group of patients. Therapy causes side effects in 75% of patients. Aside from that, 1-3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Treatment of pediatric ALL wasn’t improved by the introduction of new drugs, but by decreasing the side effects of the drugs which are already included in existing protocols. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. Glucocorticoid drugs (GC) are used in the initial phase of childhood ALL treatment, in the phase of remission induction therapy. From the beginning of the treatment until day 8, GCs are exclusively applied. Pharmacogenomic and pharmacotranscriptomic studies for GC drugs have yet to produce an algorithm that could be applied in childhood ALL treatment. Therefore, it is of extreme importance to continue researching pharmacogenomic and pharmacotranscriptomic markers relevant to the success of the GC therapy of children with ALL. Understanding the molecular mechanism of action of GC can lead to discovery of new markers that could be used for the optimization of GC therapy. New technologies, such as next generation sequencing (NGS) have created a possibility for designing panels for pharmacogenomic and pharmacotranscriptomic markers of response to different drugs. Utilization of these panels in population pharmacogenomic studies can lead to new knowledge that could open wide the doors to predictive pharmacogenomic testing...
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Farmakogenomski i farmakotranskriptomski markeri odgovora na terapiju glukokortikoidnim lekovima kod dece sa akutnom limfoblastnom leukemijom: molekularni mehanizmi delovanja, klinički i populacioni aspekti
T1  - Pharmacogenomic and pharmacotranscriptomic markers in glucocorticoid treatment of pediatric acute lymphoblastic leukemia: molecular mechanism of action, clinical and population aspects
UR  - https://hdl.handle.net/21.15107/rcub_nardus_11509
ER  - 

@phdthesis{
author = "Gašić, Vladimir",
year = "2019",
abstract = "Personalizovana medicina, medicina XXI veka, nastoji da individualizuje terapiju za svakog pacijenta, kako bi lečenje bilo što efikasnije i sa što manje rizika od toksičnosti. Personalizovana medicina se danas najviše oslanja na farmakogenomiku i farmakotranskriptomiku, koje su već dale svoj doprinos unapređenju lečenja mnogih bolesti, a posebno maligniteta. Akutna limfoblastna leukemija (ALL) predstavlja najčešći hematološki malignitet pedijatrijskog uzrasta. Mada stopa izlečenja dostiže 80-90%, ALL je i dalje glavni uzrok mortaliteta u ovih pacijenata. Terapija izaziva neželjene efekte u 75% pacijenata. Pored toga, u 1-3% pedijatrijskih pacijenata sa ALL smrtni ishod nije posledica bolesti, već je uzrokovan terapijom. Lečenje pedijatrijske ALL nije napredovalo uvođenjem novih lekova, već nastojanjem da se smanje neželjena dejstva onih lekova koji su već sastavni delovi postojećih terapijskih protokola, zbog čega su farmakogenomika i farmakotranskriptomika dobile ključno mesto u ovoj oblasti. Glukokortikoidni lekovi (GK) se koriste u početnoj fazi lečenja ALL u dece, u fazi indukcije remisije. Od početka lečenja do 8. dana se primenjuju isključivo GK. Ipak, farmakogenomske i farmakotranskriptomske studije za glukokortikoidne lekove još uvek nisu dovele do algoritma koji bi mogao biti primenjen u lečenju dečje ALL. Stoga je izuzetno značajno nastaviti sa istraživanjima farmakogenomskih i farmakotranskriptomskih markera relevantnih za uspešnost GK terapije u dece sa ALL. Razumevanje molekularnog mehanizma dejstva GK vodi ka otkrivanju novih markera koji mogu biti iskorišćeni za optimizaciju GK terapije. Nove tehnologije, kao što je sekvenciranje nove generacije (eng, next generation sequencing, NGS) su omogućile dizajniranje panela za farmakogenomske i farmakotranskriptomske markere za različite lekove..., Personalized medicine, the medicine of the XXI century, aims to individualize therapy for each patient, in order for the treatment to be as efficient and safe as possible. Today, personalized medicine is the most reliant on pharmacogenomics and pharmacotranscriptomics, which have already given their contribution to enhancing treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy of childhood. Even though the percentage of cured patients reaches 80-90%, ALL is still the main cause of mortality in this group of patients. Therapy causes side effects in 75% of patients. Aside from that, 1-3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Treatment of pediatric ALL wasn’t improved by the introduction of new drugs, but by decreasing the side effects of the drugs which are already included in existing protocols. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. Glucocorticoid drugs (GC) are used in the initial phase of childhood ALL treatment, in the phase of remission induction therapy. From the beginning of the treatment until day 8, GCs are exclusively applied. Pharmacogenomic and pharmacotranscriptomic studies for GC drugs have yet to produce an algorithm that could be applied in childhood ALL treatment. Therefore, it is of extreme importance to continue researching pharmacogenomic and pharmacotranscriptomic markers relevant to the success of the GC therapy of children with ALL. Understanding the molecular mechanism of action of GC can lead to discovery of new markers that could be used for the optimization of GC therapy. New technologies, such as next generation sequencing (NGS) have created a possibility for designing panels for pharmacogenomic and pharmacotranscriptomic markers of response to different drugs. Utilization of these panels in population pharmacogenomic studies can lead to new knowledge that could open wide the doors to predictive pharmacogenomic testing...",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Farmakogenomski i farmakotranskriptomski markeri odgovora na terapiju glukokortikoidnim lekovima kod dece sa akutnom limfoblastnom leukemijom: molekularni mehanizmi delovanja, klinički i populacioni aspekti, Pharmacogenomic and pharmacotranscriptomic markers in glucocorticoid treatment of pediatric acute lymphoblastic leukemia: molecular mechanism of action, clinical and population aspects",
url = "https://hdl.handle.net/21.15107/rcub_nardus_11509"
}

Gašić, V.. (2019). Farmakogenomski i farmakotranskriptomski markeri odgovora na terapiju glukokortikoidnim lekovima kod dece sa akutnom limfoblastnom leukemijom: molekularni mehanizmi delovanja, klinički i populacioni aspekti. 
Univerzitet u Beogradu, Biološki fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_11509

Gašić V. Farmakogenomski i farmakotranskriptomski markeri odgovora na terapiju glukokortikoidnim lekovima kod dece sa akutnom limfoblastnom leukemijom: molekularni mehanizmi delovanja, klinički i populacioni aspekti. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_11509 .

Gašić, Vladimir, "Farmakogenomski i farmakotranskriptomski markeri odgovora na terapiju glukokortikoidnim lekovima kod dece sa akutnom limfoblastnom leukemijom: molekularni mehanizmi delovanja, klinički i populacioni aspekti" (2019),
https://hdl.handle.net/21.15107/rcub_nardus_11509 .

TY  - JOUR
AU  - Skakić, Anita
AU  - Đorđević, M.
AU  - Sarajlija, A.
AU  - Klaassen, Kristel
AU  - Tošić, Nataša
AU  - Kecman, B.
AU  - Ugrin, Milena
AU  - Spasovski, Vesna
AU  - Pavlović, Sonja
AU  - Stojiljković, Maja
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1165
AB  - Glycogen storage disease (GSD) type I is inborn metabolic disease characterized by accumulation of glycogen in multiple organs. We analyzed 38 patients with clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We identified 28 GSD Ib and 5 GSD Ia patients. In 5 patients, GSD III, VI, IX, cholesteryl-ester storage disease and Shwachman-Diamond syndrome diagnoses were set using NGS. Incidences for GSD Ia and GSD Ib were estimated at 1:172746 and 1:60461 live-births, respectively. Two variants were identified in G6PC gene: c.247C gt T (p.Arg83Cys) and c.518T gt C (p.Leu173Pro). In SLC37A4 gene, 6 variants were detected. Three previously reported variants c.81T gt A (p.Asn27Lys), c.162C gt A (p.Ser54Arg) and c.1042_1043delCT (p.Leu348Valfs*53) accounted for 87% of all analyzed alleles. Computational, transcription studies and/or clinical presentation in patients confirmed pathogenic effect of 3 novel variants: c.248G gt A (p.Gly83Glu), c.404G gt A (p.Gly135Asp) and c.785G gt A (p.Ser263Glyfs*33 or p.Gly262Asp). In the cohort, hepatomegaly, hypoglycemia and failure to thrive were the most frequent presenting signs of GSD Ia, while hepatomegaly and recurrent bacterial infections were clinical hallmarks of GSD Ib. All GSD Ib patients developed neutropenia while 20.6% developed inflammatory bowel disease. Our study revealed the highest worldwide incidence of GSD Ib. Furthermore, description of 3 novel variants will facilitate medical genetic practice.
PB  - Wiley, Hoboken
T2  - Clinical Genetics
T1  - Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants
EP  - 355
IS  - 2
SP  - 350
VL  - 93
DO  - 10.1111/cge.13093
ER  - 

@article{
author = "Skakić, Anita and Đorđević, M. and Sarajlija, A. and Klaassen, Kristel and Tošić, Nataša and Kecman, B. and Ugrin, Milena and Spasovski, Vesna and Pavlović, Sonja and Stojiljković, Maja",
year = "2018",
abstract = "Glycogen storage disease (GSD) type I is inborn metabolic disease characterized by accumulation of glycogen in multiple organs. We analyzed 38 patients with clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We identified 28 GSD Ib and 5 GSD Ia patients. In 5 patients, GSD III, VI, IX, cholesteryl-ester storage disease and Shwachman-Diamond syndrome diagnoses were set using NGS. Incidences for GSD Ia and GSD Ib were estimated at 1:172746 and 1:60461 live-births, respectively. Two variants were identified in G6PC gene: c.247C gt T (p.Arg83Cys) and c.518T gt C (p.Leu173Pro). In SLC37A4 gene, 6 variants were detected. Three previously reported variants c.81T gt A (p.Asn27Lys), c.162C gt A (p.Ser54Arg) and c.1042_1043delCT (p.Leu348Valfs*53) accounted for 87% of all analyzed alleles. Computational, transcription studies and/or clinical presentation in patients confirmed pathogenic effect of 3 novel variants: c.248G gt A (p.Gly83Glu), c.404G gt A (p.Gly135Asp) and c.785G gt A (p.Ser263Glyfs*33 or p.Gly262Asp). In the cohort, hepatomegaly, hypoglycemia and failure to thrive were the most frequent presenting signs of GSD Ia, while hepatomegaly and recurrent bacterial infections were clinical hallmarks of GSD Ib. All GSD Ib patients developed neutropenia while 20.6% developed inflammatory bowel disease. Our study revealed the highest worldwide incidence of GSD Ib. Furthermore, description of 3 novel variants will facilitate medical genetic practice.",
publisher = "Wiley, Hoboken",
journal = "Clinical Genetics",
title = "Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants",
pages = "355-350",
number = "2",
volume = "93",
doi = "10.1111/cge.13093"
}

Skakić, A., Đorđević, M., Sarajlija, A., Klaassen, K., Tošić, N., Kecman, B., Ugrin, M., Spasovski, V., Pavlović, S.,& Stojiljković, M.. (2018). Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants. in Clinical Genetics
Wiley, Hoboken., 93(2), 350-355.
https://doi.org/10.1111/cge.13093

Skakić A, Đorđević M, Sarajlija A, Klaassen K, Tošić N, Kecman B, Ugrin M, Spasovski V, Pavlović S, Stojiljković M. Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants. in Clinical Genetics. 2018;93(2):350-355.
doi:10.1111/cge.13093 .

Skakić, Anita, Đorđević, M., Sarajlija, A., Klaassen, Kristel, Tošić, Nataša, Kecman, B., Ugrin, Milena, Spasovski, Vesna, Pavlović, Sonja, Stojiljković, Maja, "Genetic characterization of GSD I in Serbian population revealed unexpectedly high incidence of GSD Ib and 3 novel SLC37A4 variants" in Clinical Genetics, 93, no. 2 (2018):350-355,
https://doi.org/10.1111/cge.13093 . .

TY  - JOUR
AU  - Karan-Đurašević, Teodora
AU  - Đorđević, Maja
AU  - Skakić, Anita
AU  - Desviat, Lourdes R.
AU  - Pavlović, Sonja
AU  - Perez, Belen
AU  - Stojiljković, Maja
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1140
AB  - Treatment with tetrahydrobiopterin (BH4) is the latest therapeutic option approved for patients with phenylketonuria (PKU)-one of the most frequent inborn metabolic diseases. PKU or phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene. Given that some PAH mutations are responsive to BH4 treatment while others are non-responsive, for every novel mutation that is discovered it is essential to confirm its pathogenic effect and to assess its responsiveness to a BH4 treatment in vitro, before the drug is administered to patients. We found a c.676C gt A (p.Gln226Lys) mutation in the PAH gene in two unrelated patients with PKU. The corresponding aberrant protein has never been functionally characterized in vitro and its response to BH4 treatment is unknown. Computational analyses proposed that glutamine at position 226 is an important, evolutionary conserved amino acid while the substitution with lysine probably disturbs tertiary protein structure and impacts posttranslational PAH modifications. Using hepatoma cellular model, we demonstrated that the amount of mutant p.Gln226Lys PAH detected by Western blot was only 1.2% in comparison to wild-type PAH. The addition of sepiapterin, intracellular precursor of BH4, did not increase PAH protein yield thus marking p.Gln226Lys as BH4-non-responsive mutation. Therefore, computational, experimental, and clinical data were all in accordance showing that p.Gln226Lys is a severe pathogenic PAH mutation. Its non-responsiveness to BH4 treatment in hepatoma cellular model should be considered when deciding treatment options for PKU patients carrying this mutation. Consequently, our study will facilitate clinical genetic practice, particularly genotype-based stratification of PKU treatment.
PB  - Springer/Plenum Publishers, New York
T2  - Biochemical Genetics
T1  - Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in Hepatoma Cellular Model
EP  - 541
IS  - 5
SP  - 533
VL  - 56
DO  - 10.1007/s10528-018-9858-5
ER  - 

@article{
author = "Karan-Đurašević, Teodora and Đorđević, Maja and Skakić, Anita and Desviat, Lourdes R. and Pavlović, Sonja and Perez, Belen and Stojiljković, Maja",
year = "2018",
abstract = "Treatment with tetrahydrobiopterin (BH4) is the latest therapeutic option approved for patients with phenylketonuria (PKU)-one of the most frequent inborn metabolic diseases. PKU or phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene. Given that some PAH mutations are responsive to BH4 treatment while others are non-responsive, for every novel mutation that is discovered it is essential to confirm its pathogenic effect and to assess its responsiveness to a BH4 treatment in vitro, before the drug is administered to patients. We found a c.676C gt A (p.Gln226Lys) mutation in the PAH gene in two unrelated patients with PKU. The corresponding aberrant protein has never been functionally characterized in vitro and its response to BH4 treatment is unknown. Computational analyses proposed that glutamine at position 226 is an important, evolutionary conserved amino acid while the substitution with lysine probably disturbs tertiary protein structure and impacts posttranslational PAH modifications. Using hepatoma cellular model, we demonstrated that the amount of mutant p.Gln226Lys PAH detected by Western blot was only 1.2% in comparison to wild-type PAH. The addition of sepiapterin, intracellular precursor of BH4, did not increase PAH protein yield thus marking p.Gln226Lys as BH4-non-responsive mutation. Therefore, computational, experimental, and clinical data were all in accordance showing that p.Gln226Lys is a severe pathogenic PAH mutation. Its non-responsiveness to BH4 treatment in hepatoma cellular model should be considered when deciding treatment options for PKU patients carrying this mutation. Consequently, our study will facilitate clinical genetic practice, particularly genotype-based stratification of PKU treatment.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Biochemical Genetics",
title = "Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in Hepatoma Cellular Model",
pages = "541-533",
number = "5",
volume = "56",
doi = "10.1007/s10528-018-9858-5"
}

Karan-Đurašević, T., Đorđević, M., Skakić, A., Desviat, L. R., Pavlović, S., Perez, B.,& Stojiljković, M.. (2018). Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in Hepatoma Cellular Model. in Biochemical Genetics
Springer/Plenum Publishers, New York., 56(5), 533-541.
https://doi.org/10.1007/s10528-018-9858-5

Karan-Đurašević T, Đorđević M, Skakić A, Desviat LR, Pavlović S, Perez B, Stojiljković M. Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in Hepatoma Cellular Model. in Biochemical Genetics. 2018;56(5):533-541.
doi:10.1007/s10528-018-9858-5 .

Karan-Đurašević, Teodora, Đorđević, Maja, Skakić, Anita, Desviat, Lourdes R., Pavlović, Sonja, Perez, Belen, Stojiljković, Maja, "Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in Hepatoma Cellular Model" in Biochemical Genetics, 56, no. 5 (2018):533-541,
https://doi.org/10.1007/s10528-018-9858-5 . .

TY  - JOUR
AU  - Marjanović, Irena
AU  - Perić, Jelena
AU  - Stanić, Bojana
AU  - Pejanović, Nadja
AU  - Lucić, Bojana
AU  - Karan-Đurašević, Teodora
AU  - Janić, Dragana
AU  - Dokmanović, Lidija
AU  - Janković, Srdja
AU  - Suvajdžić-Vuković, Nada
AU  - Tomin, Dragica
AU  - Perisić, Ognjen
AU  - Rakocević, Goran
AU  - Popović, Milos
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/932
AB  - The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 x per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.
PB  - Sage Publications Ltd, London
T2  - Tumor Biology
T1  - Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease
EP  - 13401
IS  - 10
SP  - 13391
VL  - 37
DO  - 10.1007/s13277-016-5142-7
ER  - 

@article{
author = "Marjanović, Irena and Perić, Jelena and Stanić, Bojana and Pejanović, Nadja and Lucić, Bojana and Karan-Đurašević, Teodora and Janić, Dragana and Dokmanović, Lidija and Janković, Srdja and Suvajdžić-Vuković, Nada and Tomin, Dragica and Perisić, Ognjen and Rakocević, Goran and Popović, Milos and Pavlović, Sonja and Tošić, Nataša",
year = "2016",
abstract = "The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 x per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.",
publisher = "Sage Publications Ltd, London",
journal = "Tumor Biology",
title = "Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease",
pages = "13401-13391",
number = "10",
volume = "37",
doi = "10.1007/s13277-016-5142-7"
}

Marjanović, I., Perić, J., Stanić, B., Pejanović, N., Lucić, B., Karan-Đurašević, T., Janić, D., Dokmanović, L., Janković, S., Suvajdžić-Vuković, N., Tomin, D., Perisić, O., Rakocević, G., Popović, M., Pavlović, S.,& Tošić, N.. (2016). Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease. in Tumor Biology
Sage Publications Ltd, London., 37(10), 13391-13401.
https://doi.org/10.1007/s13277-016-5142-7

Marjanović I, Perić J, Stanić B, Pejanović N, Lucić B, Karan-Đurašević T, Janić D, Dokmanović L, Janković S, Suvajdžić-Vuković N, Tomin D, Perisić O, Rakocević G, Popović M, Pavlović S, Tošić N. Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease. in Tumor Biology. 2016;37(10):13391-13401.
doi:10.1007/s13277-016-5142-7 .

Marjanović, Irena, Perić, Jelena, Stanić, Bojana, Pejanović, Nadja, Lucić, Bojana, Karan-Đurašević, Teodora, Janić, Dragana, Dokmanović, Lidija, Janković, Srdja, Suvajdžić-Vuković, Nada, Tomin, Dragica, Perisić, Ognjen, Rakocević, Goran, Popović, Milos, Pavlović, Sonja, Tošić, Nataša, "Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease" in Tumor Biology, 37, no. 10 (2016):13391-13401,
https://doi.org/10.1007/s13277-016-5142-7 . .

TY  - JOUR
AU  - Stojiljković, Maja
AU  - Karan-Đurašević, Teodora
AU  - Đorđević, M.
AU  - Sarajlija, A.
AU  - Brasil, S.
AU  - Kecman, B.
AU  - Grković, S.
AU  - Kostić, Jelena
AU  - Rodriguez-Pombo, P.
AU  - Desviat, L. R.
AU  - Pavlović, Sonja
AU  - Perez, B.
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/907
AB  - Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South-Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases.
PB  - Wiley, Hoboken
T2  - Clinical Genetics
T1  - Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias
EP  - 257
IS  - 3
SP  - 252
VL  - 90
DO  - 10.1111/cge.12751
ER  - 

@article{
author = "Stojiljković, Maja and Karan-Đurašević, Teodora and Đorđević, M. and Sarajlija, A. and Brasil, S. and Kecman, B. and Grković, S. and Kostić, Jelena and Rodriguez-Pombo, P. and Desviat, L. R. and Pavlović, Sonja and Perez, B.",
year = "2016",
abstract = "Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South-Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases.",
publisher = "Wiley, Hoboken",
journal = "Clinical Genetics",
title = "Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias",
pages = "257-252",
number = "3",
volume = "90",
doi = "10.1111/cge.12751"
}

Stojiljković, M., Karan-Đurašević, T., Đorđević, M., Sarajlija, A., Brasil, S., Kecman, B., Grković, S., Kostić, J., Rodriguez-Pombo, P., Desviat, L. R., Pavlović, S.,& Perez, B.. (2016). Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias. in Clinical Genetics
Wiley, Hoboken., 90(3), 252-257.
https://doi.org/10.1111/cge.12751

Stojiljković M, Karan-Đurašević T, Đorđević M, Sarajlija A, Brasil S, Kecman B, Grković S, Kostić J, Rodriguez-Pombo P, Desviat LR, Pavlović S, Perez B. Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias. in Clinical Genetics. 2016;90(3):252-257.
doi:10.1111/cge.12751 .

Stojiljković, Maja, Karan-Đurašević, Teodora, Đorđević, M., Sarajlija, A., Brasil, S., Kecman, B., Grković, S., Kostić, Jelena, Rodriguez-Pombo, P., Desviat, L. R., Pavlović, Sonja, Perez, B., "Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias" in Clinical Genetics, 90, no. 3 (2016):252-257,
https://doi.org/10.1111/cge.12751 . .

TY  - JOUR
AU  - Todorovic-Balint, Milena
AU  - Jelicić, Jelena
AU  - Mihaljević, Biljana
AU  - Kostić, Jelena
AU  - Stanić, Bojana
AU  - Balint, Bela
AU  - Pejanović, Nadja
AU  - Lucić, Bojana
AU  - Tošić, Nataša
AU  - Marjanović, Irena
AU  - Stojiljković, Maja
AU  - Karan-Đurašević, Teodora
AU  - Perisić, Ognjen
AU  - Rakocević, Goran
AU  - Popović, Milos
AU  - Raicević, Sava
AU  - Bila, Jelena
AU  - Antić, Darko
AU  - Anđelić, Boško
AU  - Pavlović, Sonja
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/936
AB  - The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
IS  - 5
VL  - 17
DO  - 10.3390/ijms17050683
ER  - 

@article{
author = "Todorovic-Balint, Milena and Jelicić, Jelena and Mihaljević, Biljana and Kostić, Jelena and Stanić, Bojana and Balint, Bela and Pejanović, Nadja and Lucić, Bojana and Tošić, Nataša and Marjanović, Irena and Stojiljković, Maja and Karan-Đurašević, Teodora and Perisić, Ognjen and Rakocević, Goran and Popović, Milos and Raicević, Sava and Bila, Jelena and Antić, Darko and Anđelić, Boško and Pavlović, Sonja",
year = "2016",
abstract = "The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses",
number = "5",
volume = "17",
doi = "10.3390/ijms17050683"
}

Todorovic-Balint, M., Jelicić, J., Mihaljević, B., Kostić, J., Stanić, B., Balint, B., Pejanović, N., Lucić, B., Tošić, N., Marjanović, I., Stojiljković, M., Karan-Đurašević, T., Perisić, O., Rakocević, G., Popović, M., Raicević, S., Bila, J., Antić, D., Anđelić, B.,& Pavlović, S.. (2016). Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses. in International Journal of Molecular Sciences
MDPI, Basel., 17(5).
https://doi.org/10.3390/ijms17050683

Todorovic-Balint M, Jelicić J, Mihaljević B, Kostić J, Stanić B, Balint B, Pejanović N, Lucić B, Tošić N, Marjanović I, Stojiljković M, Karan-Đurašević T, Perisić O, Rakocević G, Popović M, Raicević S, Bila J, Antić D, Anđelić B, Pavlović S. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses. in International Journal of Molecular Sciences. 2016;17(5).
doi:10.3390/ijms17050683 .

Todorovic-Balint, Milena, Jelicić, Jelena, Mihaljević, Biljana, Kostić, Jelena, Stanić, Bojana, Balint, Bela, Pejanović, Nadja, Lucić, Bojana, Tošić, Nataša, Marjanović, Irena, Stojiljković, Maja, Karan-Đurašević, Teodora, Perisić, Ognjen, Rakocević, Goran, Popović, Milos, Raicević, Sava, Bila, Jelena, Antić, Darko, Anđelić, Boško, Pavlović, Sonja, "Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses" in International Journal of Molecular Sciences, 17, no. 5 (2016),
https://doi.org/10.3390/ijms17050683 . .