Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

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...

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Main Authors: 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
Format: Online
Language:English
Published: MDPI 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881509/
id pubmed-4881509
recordtype oai_dc
spelling pubmed-48815092016-05-27 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 Article 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. MDPI 2016-05-06 /pmc/articles/PMC4881509/ /pubmed/27164089 http://dx.doi.org/10.3390/ijms17050683 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author 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
spellingShingle 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
Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
author_facet 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
author_sort Todorovic Balint, Milena
title Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
title_short Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
title_full Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
title_fullStr Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
title_full_unstemmed Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
title_sort gene mutation profiles in primary diffuse large b cell lymphoma of central nervous system: next generation sequencing analyses
description 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
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881509/
_version_ 1613584657354326016

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