Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
2016
Preuzimanje 🢃
Autori
Todorovic-Balint, MilenaJelicić, 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
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 ear...lier 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.
Ključne reči:
TP53 / SMO / PTEN / primary DLBCL CNS / ATMIzvor:
International Journal of Molecular Sciences, 2016, 17, 5Izdavač:
- MDPI, Basel
Finansiranje / projekti:
- Retke bolesti: molekularna patofiziologija, dijagnostički i terapijski modaliteti i socijalni, etički i pravni aspekti (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
- Strengthening the Research Potential of IMGGE through Reinforcement of Biomedical Science of Rare Diseases in Serbia - en route for innovation (EU-FP7-316088)
DOI: 10.3390/ijms17050683
ISSN: 1422-0067
PubMed: 27164089
WoS: 000378791400077
Scopus: 2-s2.0-84966309019
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .