Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer.
Adenomatous Polyposis Coli Protein
Adult
Age Factors
Biomarkers, Tumor
/ genetics
Class I Phosphatidylinositol 3-Kinases
/ genetics
Cohort Studies
Colorectal Neoplasms
/ epidemiology
Female
Genomics
/ methods
Humans
Male
Microsatellite Instability
Middle Aged
Mutation
Neoplasm Staging
Proto-Oncogene Proteins B-raf
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
Smad4 Protein
/ genetics
Tumor Suppressor Protein p53
/ genetics
United States
/ epidemiology
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 10 2019
01 10 2019
Historique:
received:
18
03
2019
revised:
03
05
2019
accepted:
21
06
2019
pubmed:
28
6
2019
medline:
26
9
2020
entrez:
28
6
2019
Statut:
ppublish
Résumé
The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer. DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established. Overall genomic alteration rates in the younger (<40) and older (≥50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biology and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer.
Identifiants
pubmed: 31243121
pii: 1078-0432.CCR-19-0899
doi: 10.1158/1078-0432.CCR-19-0899
pmc: PMC6774873
mid: NIHMS1533033
doi:
Substances chimiques
APC protein, human
0
Adenomatous Polyposis Coli Protein
0
Biomarkers, Tumor
0
KRAS protein, human
0
SMAD4 protein, human
0
Smad4 Protein
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
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
5852-5858Subventions
Organisme : NCI NIH HHS
ID : P30 CA006927
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229259
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108195
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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