Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer.
NGS
genes
mCRC
molecular stratification
mutation
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
10
2019
accepted:
27
03
2020
entrez:
28
5
2020
pubmed:
28
5
2020
medline:
28
5
2020
Statut:
epublish
Résumé
Extensive molecular characterization of human colorectal cancer (CRC) via Next Generation Sequencing (NGS) indicated that genetic or epigenetic dysregulation of a relevant, but limited, number of molecular pathways typically occurs in this tumor. The molecular picture of the disease is significantly complicated by the frequent occurrence of individually rare genetic aberrations, which expand tumor heterogeneity. Inter- and intratumor molecular heterogeneity is very likely responsible for the remarkable individual variability in the response to conventional and target-driven first-line therapies, in metastatic CRC (mCRC) patients, whose median overall survival remains unsatisfactory. Implementation of an extensive molecular characterization of mCRC in the clinical routine does not yet appear feasible on a large scale, while multigene panel sequencing of most commonly mutated oncogene/oncosuppressor hotspots is more easily achievable. Here, we report that clinical multigene panel sequencing performed for anti-EGFR therapy predictive purposes in 639 formalin-fixed paraffin-embedded (FFPE) mCRC specimens revealed previously unknown pairwise mutation associations and a high proportion of cases carrying actionable gene mutations. Most importantly, a simple principal component analysis directed the delineation of a new molecular stratification of mCRC patients in eight groups characterized by non-random, specific mutational association patterns (MAPs), aggregating samples with similar biology. These data were validated on a The Cancer Genome Atlas (TCGA) CRC dataset. The proposed stratification may provide great opportunities to direct more informed therapeutic decisions in the majority of mCRC cases.
Identifiants
pubmed: 32457828
doi: 10.3389/fonc.2020.00560
pmc: PMC7221020
doi:
Types de publication
Journal Article
Langues
eng
Pagination
560Informations de copyright
Copyright © 2020 Belardinilli, Capalbo, Malapelle, Pisapia, Raimondo, Milanetti, Yasaman, Liccardi, Paci, Sibilio, Pepe, Bonfiglio, Mezi, Magri, Coppa, Nicolussi, Gradilone, Petroni, Di Giulio, Fabretti, Infante, Coni, Canettieri, Troncone and Giannini.
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