title: Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses.
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.
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. bb.lena@gmail.com.|Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. bb.lena@gmail.com.
authors.forename: Milena
authors.initials: M
authors.lastname: Todorovic Balint
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. jecajelicic@yahoo.com.
authors.forename: Jelena
authors.initials: J
authors.lastname: Jelicic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. zmzg@sezampro.rs.|Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. zmzg@sezampro.rs.
authors.forename: Biljana
authors.initials: B
authors.lastname: Mihaljevic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. kostichelena@gmail.com.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kostic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. bojanastanic@yahoo.com.
authors.forename: Bojana
authors.initials: B
authors.lastname: Stanic
authors.affiliation: Institute of Transfusiology and Hemobiology of Military Medical Academy, Belgrade 11000, Serbia. belabalint26@yahoo.com.
authors.forename: Bela
authors.initials: B
authors.lastname: Balint
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. nadjapejanovic@gmail.com.
authors.forename: Nadja
authors.initials: N
authors.lastname: Pejanovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. lucic.bojana@gmail.com.
authors.forename: Bojana
authors.initials: B
authors.lastname: Lucic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. nmtosic@sezampro.rs.
authors.forename: Natasa
authors.initials: N
authors.lastname: Tosic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. irenas24@gmail.com.
authors.forename: Irena
authors.initials: I
authors.lastname: Marjanovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. maja.stojiljkovic@yahoo.com.
authors.forename: Maja
authors.initials: M
authors.lastname: Stojiljkovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. dora_karan@yahoo.com.
authors.forename: Teodora
authors.initials: T
authors.lastname: Karan-Djurasevic
authors.affiliation: Seven Bridges Genomics, Belgrade 11000, Serbia. ognjen.perisic@gmail.com.
authors.forename: Ognjen
authors.initials: O
authors.lastname: Perisic
authors.affiliation: Seven Bridges Genomics, Belgrade 11000, Serbia. goran.rakocevic@sbgenomics.com.
authors.forename: Goran
authors.initials: G
authors.lastname: Rakocevic
authors.affiliation: Seven Bridges Genomics, Belgrade 11000, Serbia. milos.popovic@sbgenomics.com.
authors.forename: Milos
authors.initials: M
authors.lastname: Popovic
authors.affiliation: Department of Histopathology, Clinical Center of Serbia, Belgrade 11000, Serbia. jjelicic86@gmail.com.
authors.forename: Sava
authors.initials: S
authors.lastname: Raicevic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. idabakrac123@gmail.com.|Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. idabakrac123@gmail.com.
authors.forename: Jelena
authors.initials: J
authors.lastname: Bila
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. milosmak13@gmail.com.|Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. milosmak13@gmail.com.
authors.forename: Darko
authors.initials: D
authors.lastname: Antic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia. belab@imi.bg.ac.rs.|Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia. belab@imi.bg.ac.rs.
authors.forename: Bosko
authors.initials: B
authors.lastname: Andjelic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade 11010, Serbia. sonya@sezampro.rs.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics
chemical_list: D015513:Oncogene Proteins
keywords: ATM; PTEN; SMO; TP53; primary DLBCL CNS