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Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses.
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.
Afiliación
  • Todorovic Balint M; Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. bb.lena@gmail.com.
  • Jelicic J; Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. bb.lena@gmail.com.
  • Mihaljevic B; Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. jecajelicic@yahoo.com.
  • Kostic J; Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. zmzg@sezampro.rs.
  • Stanic B; Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. zmzg@sezampro.rs.
  • Balint B; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. kostichelena@gmail.com.
  • Pejanovic N; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. bojanastanic@yahoo.com.
  • Lucic B; Institute of Transfusiology and Hemobiology of Military Medical Academy, Belgrade 11000, Serbia. belabalint26@yahoo.com.
  • Tosic N; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. nadjapejanovic@gmail.com.
  • Marjanovic I; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. lucic.bojana@gmail.com.
  • Stojiljkovic M; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. nmtosic@sezampro.rs.
  • Karan-Djurasevic T; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. irenas24@gmail.com.
  • Perisic O; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. maja.stojiljkovic@yahoo.com.
  • Rakocevic G; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. dora_karan@yahoo.com.
  • Popovic M; Seven Bridges Genomics, Belgrade 11000, Serbia. ognjen.perisic@gmail.com.
  • Raicevic S; Seven Bridges Genomics, Belgrade 11000, Serbia. goran.rakocevic@sbgenomics.com.
  • Bila J; Seven Bridges Genomics, Belgrade 11000, Serbia. milos.popovic@sbgenomics.com.
  • Antic D; Department of Histopathology, Clinical Center of Serbia, Belgrade 11000, Serbia. jjelicic86@gmail.com.
  • Andjelic B; Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. idabakrac123@gmail.com.
  • Pavlovic S; Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. idabakrac123@gmail.com.
Int J Mol Sci ; 17(5)2016 May 06.
Article en En | MEDLINE | ID: mdl-27164089
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Neoplasias del Sistema Nervioso Central / Mutación Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2016 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Neoplasias del Sistema Nervioso Central / Mutación Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2016 Tipo del documento: Article Pais de publicación: Suiza