Mutational Analysis of Primary Central Nervous System Lymphoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Jun 28

PMID 24970810

Citations 78

Authors

Aurelie Bruno

Blandine Boisselier

Karim Labreche

Yannick Marie

Marc Polivka

Anne Jouvet

Clovis Adam

Dominique Figarella-Branger

Catherine Miquel

Sandrine Eimer

Caroline Houillier

Carole Soussain

Karima Mokhtari

Romain Daveau

Khe Hoang-Xuan

Affiliations

Soon will be listed here.

Abstract

Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.

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