In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment
Аутори
Gašić, VladimirKotur, Nikola
Stanković, Biljana
Pavlović, Đorđe
Jelovac, Marina
Perić, Jelena
Ristivojević, Bojan
Pavlović, Sonja
Zukić, Branka
Остала ауторства
Morić, IvanaĐorđević, Valentina
Конференцијски прилог (Објављена верзија)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт
Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side
effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due
to treatment. More efficient treatment of pediatric ALL has been developed by avoiding
drug adverse effects included in the treatment protocols. Therefore, implementation of
pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing
(NGS) contributed to discovery of novel genetic markers, potential candidates for targeted
therapy and predictors of efficacy and toxicity of drugs.
We aimed to discover novel potential pharmacogenomic markers in pediatric ALL.
DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using
the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48
oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne
(Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC
r...esponse markers was designed. Predicting the effects of novel variants was performed
using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability
and modeling we used STRUM method and i-TASSER server.
In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been
identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T
possess potential as pharmacogenomic markers, therefore, they are candidates for
molecular targeted therapy. In the exome sequencing study, according to the prediction
algorithms, 3 new potential markers in pharmacogenes related to GC response have been
identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812.
Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations,
candidates for targeted molecular therapy, as well as 3 novel germinative variants,
potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic
profiling of each pediatric ALL patient is indispensable for new therapy approaches and it
could lead to better outcomes.
Кључне речи:
pediatric / acute lymphoblastic leukemia / pharmacogenomicsИзвор:
4th Belgrade Bioinformatics Conference, 2023, 4, 95-95Издавач:
- Belgrade : Institute of molecular genetics and genetic engineering
Финансирање / пројекти:
- This research was funded by the PharmGenHUB Project 101059870, Twinning Western Balkan call: HORIZON-WIDERA-2021-ACCESS-02
Напомена:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Gašić, Vladimir AU - Kotur, Nikola AU - Stanković, Biljana AU - Pavlović, Đorđe AU - Jelovac, Marina AU - Perić, Jelena AU - Ristivojević, Bojan AU - Pavlović, Sonja AU - Zukić, Branka PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2040 AB - Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due to treatment. More efficient treatment of pediatric ALL has been developed by avoiding drug adverse effects included in the treatment protocols. Therefore, implementation of pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing (NGS) contributed to discovery of novel genetic markers, potential candidates for targeted therapy and predictors of efficacy and toxicity of drugs. We aimed to discover novel potential pharmacogenomic markers in pediatric ALL. DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48 oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne (Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC response markers was designed. Predicting the effects of novel variants was performed using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability and modeling we used STRUM method and i-TASSER server. In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T possess potential as pharmacogenomic markers, therefore, they are candidates for molecular targeted therapy. In the exome sequencing study, according to the prediction algorithms, 3 new potential markers in pharmacogenes related to GC response have been identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812. Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations, candidates for targeted molecular therapy, as well as 3 novel germinative variants, potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic profiling of each pediatric ALL patient is indispensable for new therapy approaches and it could lead to better outcomes. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment EP - 95 SP - 95 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_2040 ER -
@conference{ author = "Gašić, Vladimir and Kotur, Nikola and Stanković, Biljana and Pavlović, Đorđe and Jelovac, Marina and Perić, Jelena and Ristivojević, Bojan and Pavlović, Sonja and Zukić, Branka", year = "2023", abstract = "Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due to treatment. More efficient treatment of pediatric ALL has been developed by avoiding drug adverse effects included in the treatment protocols. Therefore, implementation of pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing (NGS) contributed to discovery of novel genetic markers, potential candidates for targeted therapy and predictors of efficacy and toxicity of drugs. We aimed to discover novel potential pharmacogenomic markers in pediatric ALL. DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48 oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne (Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC response markers was designed. Predicting the effects of novel variants was performed using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability and modeling we used STRUM method and i-TASSER server. In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T possess potential as pharmacogenomic markers, therefore, they are candidates for molecular targeted therapy. In the exome sequencing study, according to the prediction algorithms, 3 new potential markers in pharmacogenes related to GC response have been identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812. Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations, candidates for targeted molecular therapy, as well as 3 novel germinative variants, potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic profiling of each pediatric ALL patient is indispensable for new therapy approaches and it could lead to better outcomes.", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment", pages = "95-95", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_2040" }
Gašić, V., Kotur, N., Stanković, B., Pavlović, Đ., Jelovac, M., Perić, J., Ristivojević, B., Pavlović, S.,& Zukić, B.. (2023). In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 95-95. https://hdl.handle.net/21.15107/rcub_imagine_2040
Gašić V, Kotur N, Stanković B, Pavlović Đ, Jelovac M, Perić J, Ristivojević B, Pavlović S, Zukić B. In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment. in 4th Belgrade Bioinformatics Conference. 2023;4:95-95. https://hdl.handle.net/21.15107/rcub_imagine_2040 .
Gašić, Vladimir, Kotur, Nikola, Stanković, Biljana, Pavlović, Đorđe, Jelovac, Marina, Perić, Jelena, Ristivojević, Bojan, Pavlović, Sonja, Zukić, Branka, "In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment" in 4th Belgrade Bioinformatics Conference, 4 (2023):95-95, https://hdl.handle.net/21.15107/rcub_imagine_2040 .