Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
AbstractThe 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. View Full-Text
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Todorovic Balint, M.; Jelicic, J.; Mihaljevic, B.; Kostic, J.; Stanic, B.; Balint, B.; Pejanovic, N.; Lucic, B.; Tosic, N.; Marjanovic, I.; Stojiljkovic, M.; Karan-Djurasevic, T.; Perisic, O.; Rakocevic, G.; Popovic, M.; Raicevic, S.; Bila, J.; Antic, D.; Andjelic, B.; Pavlovic, S. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses. Int. J. Mol. Sci. 2016, 17, 683.
Todorovic Balint M, Jelicic J, Mihaljevic B, Kostic J, Stanic B, Balint B, Pejanovic N, Lucic B, Tosic N, Marjanovic I, Stojiljkovic M, Karan-Djurasevic T, Perisic O, Rakocevic G, Popovic M, Raicevic S, Bila J, Antic D, Andjelic B, Pavlovic S. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses. International Journal of Molecular Sciences. 2016; 17(5):683.Chicago/Turabian Style
Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja. 2016. "Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses." Int. J. Mol. Sci. 17, no. 5: 683.
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