Rankings
Publications
Search Publications
Cited-By Search
Sources
Publishers
Scholars
Scholars
Top Cited Scholars
Organizations
About
Login
Register
Home
Publications
Data from Recurrent Mutations of MYD88 and TBL1XR1 in Primary Central Nervous System Lymphomas
Home
Publications
Data from Recurrent Mutations of MYD88 and TBL1XR1 in Primary Central Nervous System Lymphomas
Data from Recurrent Mutations of MYD88 and TBL1XR1 in Primary Central Nervous System Lymphomas
AG
Alberto Gonzalez-Aguilar
Alberto Gonzalez-Aguilar
AI
Ahmed Idbaih
Ahmed Idbaih
BB
Blandine Boisselier
Blandine Boisselier
NH
Naïma Habbita
Naïma Habbita
MR
Marta Rossetto
Marta Rossetto
AL
Alice Laurenge
Alice Laurenge
AB
Aurélie Bruno
Aurélie Bruno
AJ
Anne Jouvet
Anne Jouvet
MP
Marc Polivka
Marc Polivka
CA
Clovis Adam
Clovis Adam
DF
Dominique Figarella-Branger
Dominique Figarella-Branger
CM
Catherine Miquel
Catherine Miquel
See more
Open Access
Publisher Website
Google Scholar
Add to library
Cite
Download
Share
Download
31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6522807.v1
Abstract
Purpose: Our objective was to identify the genetic changes involved in primary central nervous system lymphoma (PCNSL) oncogenesis and evaluate their clinical relevance.Experimental Design: We investigated a series of 29 newly diagnosed, HIV-negative, PCNSL patients using high-resolution single-nucleotide polymorphism (SNP) arrays (n = 29) and whole-exome sequencing (n = 4) approaches. Recurrent homozygous deletions and somatic gene mutations found were validated by quantitative real-time PCR and Sanger sequencing, respectively. Molecular results were correlated with prognosis.Results: All PCNSLs were diffuse large B-cell lymphomas, and the patients received chemotherapy without radiotherapy as initial treatment. The SNP analysis revealed recurrent large and focal chromosome imbalances that target candidate genes in PCNSL oncogenesis. The most frequent genomic abnormalities were (i) 6p21.32 loss (HLA locus), (ii) 6q loss, (iii) CDKN2A homozygous deletions, (iv) 12q12-q22, and (v) chromosome 7q21 and 7q31 gains. Homozygous deletions of PRMD1, TOX, and DOCK5 and the amplification of HDAC9 were also detected. Sequencing of matched tumor and blood DNA samples identified novel somatic mutations in MYD88 and TBL1XR1 in 38% and 14% of the cases, respectively. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis showed that 6q22 loss (P = 0.006 and P = 0.01) and CDKN2A homozygous deletion (P = 0.02 and P = 0.01) were significantly associated with shorter progression-free survival and overall survival.Conclusions: Our study provides new insights into the molecular tumorigenesis of PCNSL and identifies novel genetic alterations in this disease, especially MYD88 and TBL1XR1 mutations activating the NF-κB signaling pathway, which may be promising targets for future therapeutic strategies. Clin Cancer Res; 18(19); 5203–11. ©2012 AACR.
Keywords
MUTATIONS OF MYD88
PCNSL
MULTIVARIATE ANALYSIS
SOMATIC
HIV
TBL1XR1
TREATMENT
SURVIVAL
All Articles
Open Access