The Landscape of Alterations in DNA Damage Response Pathways in Colorectal Cancer.
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:
01 06 2021
01 06 2021
Historique:
received:
14
09
2020
revised:
13
01
2021
accepted:
22
03
2021
pubmed:
27
3
2021
medline:
22
3
2022
entrez:
26
3
2021
Statut:
ppublish
Résumé
Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and is associated with chemosensitivity. Although the mismatch repair system has been extensively studied, the clinical implications of other mechanisms associated with DDR alterations in patients with colorectal cancer remain unclear. This study aimed to understand DDR pathways alterations and their association with common clinical features in patients with colorectal cancer. Next-generation sequencing and whole-transcriptome sequencing were conducted using formalin-fixed paraffin-embedded samples submitted to a commercial Clinical Laboratory Improvement Amendments-certified laboratory. Samples with pathogenic or presumed pathogenic mutations in 29 specific DDR-related genes were considered as DDR-mutant (DDR-MT) and the remaining samples as DDR-wild type (DDR-WT). Of 9,321 patients with colorectal cancer, 1,290 (13.8%) were DDR-MT. The frequency of DDR-MT was significantly higher in microsatellite instability-high (MSI-H) cases than in microsatellite stable cases (76.4% vs. 9.5%). The DDR-MT genotype was higher in the right-sided, We characterized a distinct subgroup of patients with colorectal cancer with tumors harboring mutations in the DDR-related genes. These patients more commonly had MSI-H tumors and exhibited an activated immune signature regardless of their tumor's MSI status. These findings warrant further investigations to develop personalized treatment strategies in this significant subgroup of patients with colorectal cancer.
Identifiants
pubmed: 33766816
pii: 1078-0432.CCR-20-3635
doi: 10.1158/1078-0432.CCR-20-3635
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3234-3242Subventions
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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