Genetic, Epigenetic, and Immunologic Profiling of MMR-Deficient Relapsed Glioblastoma.
Biomarkers, Tumor
/ genetics
Brain
/ pathology
Brain Neoplasms
/ genetics
Chemoradiotherapy, Adjuvant
DNA Methylation
DNA Mismatch Repair
Epigenesis, Genetic
Female
Gene Expression Profiling
Genes, MHC Class I
/ genetics
Glioblastoma
/ genetics
Histocompatibility Antigens Class I
/ genetics
Humans
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
/ genetics
Progression-Free Survival
Retrospective Studies
Telomere Homeostasis
/ genetics
Tumor Microenvironment
/ genetics
Exome Sequencing
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
19
06
2018
revised:
25
09
2018
accepted:
28
11
2018
pubmed:
6
12
2018
medline:
28
5
2020
entrez:
6
12
2018
Statut:
ppublish
Résumé
In-depth characterization of recurrent glioblastoma (rGBM) might contribute to a better understanding of the mechanisms behind tumor progression and enable rGBM treatment with targeted drugs. Expression of MMR proteins was partially or completely lost in 25.9% rGBM samples. Specifically, 12 samples showed partial or total MSH6 expression reduction. Conversely, 96.4% of GBM samples at diagnosis expressed MMR markers. WES disclosed lack of variants in MMR genes in primary samples, whereas two MSH6-negative rGBM samples shared a c.3438+1G>A* splicing Multilevel profiling of MMR-deficient rGBM uncovered hypermutated genotype uncoupled from enriched expression of immune-related markers. Assessment of MHC class I expression and TMB should be included in protocols aiming to identify rGBM patients potentially eligible for treatment with drugs targeting immune-checkpoint inhibitors.
Identifiants
pubmed: 30514778
pii: 1078-0432.CCR-18-1892
doi: 10.1158/1078-0432.CCR-18-1892
doi:
Substances chimiques
Biomarkers, Tumor
0
Histocompatibility Antigens Class I
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1828-1837Informations de copyright
©2018 American Association for Cancer Research.