MYD88 L265P mutation and CDKN2A loss are early mutational events in primary central nervous system diffuse large B-cell lymphomas.
Blood Adv
; 3(3): 375-383, 2019 02 12.
Article
em En
| MEDLINE
| ID: mdl-30723112
ABSTRACT
The genetic alterations that define primary central nervous system lymphoma (PCNSL) are incompletely elucidated, and the genomic evolution from diagnosis to relapse is poorly understood. We performed whole-exome sequencing (WES) on 36 PCNSL patients and targeted MYD88 sequencing on a validation cohort of 27 PCNSL patients. We also performed WES and phylogenetic analysis of 3 matched newly diagnosed and relapsed tumor specimens and 1 synchronous intracranial and extracranial relapse. Immunohistochemistry (IHC) for programmed death-1 ligand (PD-L1) was performed on 43 patient specimens. Combined WES and targeted sequencing identified MYD88 mutation in 67% (42 of 63) of patients, CDKN2A biallelic loss in 44% (16 of 36), and CD79b mutation in 61% (22 of 36). Copy-number analysis demonstrated frequent regions of copy loss (ie, CDKN2A), with few areas of amplification. CD79b mutations were associated with improved progression-free and overall survival. We did not identify amplification at the PD-1/PD-L1 loci. IHC for PD-L1 revealed membranous expression in 30% (13 of 43) of specimens. Phylogenetic analysis of paired primary and relapsed specimens identified MYD88 mutation and CDKN2A loss as early clonal events. PCNSL is characterized by frequent mutations within the B-cell receptor and NF-κB pathways. The lack of PD-L1 amplifications, along with membranous PD-L1 expression in 30% of our cohort, suggests that PD-1/PD-L1 inhibitors may be useful in a subset of PCNSL. WES of PCNSL provides insight into the genomic landscape and evolution of this rare lymphoma subtype and potentially informs more rational treatment decisions.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfoma Difuso de Grandes Células B
/
Neoplasias do Sistema Nervoso Central
/
Inibidor p16 de Quinase Dependente de Ciclina
/
Fator 88 de Diferenciação Mieloide
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Blood Adv
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Marrocos