High prevalence of unusual KRAS, NRAS, and BRAF mutations in POLE-hypermutated colorectal cancers.
Biomarkers, Tumor
/ genetics
Colorectal Neoplasms
/ diagnosis
DNA Polymerase II
/ genetics
GTP Phosphohydrolases
/ genetics
Humans
Male
Membrane Proteins
/ genetics
Mutation
/ genetics
Poly-ADP-Ribose Binding Proteins
/ genetics
Prevalence
Proto-Oncogene Proteins B-raf
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
POLE
colorectal cancers
immunotherapy
polymerase epsilon
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
05
04
2022
received:
22
12
2021
accepted:
25
05
2022
pubmed:
29
5
2022
medline:
9
9
2022
entrez:
28
5
2022
Statut:
ppublish
Résumé
Exonucleasic domain POLE (edPOLE) mutations, which are responsible for a hypermutated tumor phenotype, occur in 1-2% of colorectal cancer (CRC) cases. These alterations represent an emerging biomarker for response to immune checkpoint blockade. This study aimed to assess the molecular characteristics of edPOLE-mutated tumors to facilitate patient screening. Based on opensource data analysis, we compared the prevalence of edPOLE mutations in a control group of unselected CRC patients (n = 222) vs a group enriched for unusual BRAF/RAS mutations (n = 198). Tumor mutational burden (TMB) and immune infiltrate of tumors harboring edPOLE mutations were then analyzed. In total, 420 CRC patients were analyzed: 11 edPOLE-mutated tumors were identified, most frequently in microsatellite (MMR)-proficient young (< 70 years) male patients, with left-sided tumors harboring noncodon 12 KRAS mutation. The prevalence of edPOLE-mutated tumors in the control vs the experimental screening group was, respectively, 0.45% (n = 1) vs 5.0% (n = 10). Among the 11 edPOLE-mutated cases, two had a low TMB, three were hypermutated, and six were ultramutated. EdPOLE-mutated cases had a high CD8
Identifiants
pubmed: 35624529
doi: 10.1002/1878-0261.13257
pmc: PMC9441000
doi:
Substances chimiques
Biomarkers, Tumor
0
KRAS protein, human
0
Membrane Proteins
0
Poly-ADP-Ribose Binding Proteins
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
DNA Polymerase II
EC 2.7.7.7
POLE protein, human
EC 2.7.7.7
GTP Phosphohydrolases
EC 3.6.1.-
NRAS protein, human
EC 3.6.1.-
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3055-3065Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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