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Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer
- Source :
- Frontiers in Oncology, Frontiers in Oncology, Vol 10 (2020), Frontiers in oncology 10 (2020). doi:10.3389/fonc.2020.00560, info:cnr-pdr/source/autori:Belardinilli F.; Capalbo C.; Malapelle U.; Pisapia P.; Raimondo D.; Milanetti E.; Yasaman M.; Liccardi C.; Paci P.; Sibilio P.; Pepe F.; Bonfiglio C.; Mezi S.; Magri V.; Coppa A.; Nicolussi A.; Gradilone A.; Petroni M.; Di Giulio S.; Fabretti F.; Infante P.; Coni S.; Canettieri G.; Troncone G.; Giannini G./titolo:Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer/doi:10.3389%2Ffonc.2020.00560/rivista:Frontiers in oncology/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:10
- Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
molecular stratification
mCRC, NGS, molecular stratification, mutation, genes
Colorectal cancer
Disease
Computational biology
Gene mutation
Biology
lcsh:RC254-282
Tumor heterogeneity
DNA sequencing
03 medical and health sciences
0302 clinical medicine
medicine
Epigenetics
gene
genes
Gene
Original Research
Oncogene
COMPUTATIONAL AND SYSTEMS BIOLOGY
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
digestive system diseases
030104 developmental biology
Oncology
mCRC
030220 oncology & carcinogenesis
NGS
mutation
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in oncology
- Accession number :
- edsair.doi.dedup.....b560ede159d7b17489e1c9b861b3f38e