Utility of exome sequencing in routine care for metastatic colorectal cancer.
RAS status
biomarkers
colorectal cancer
exome
genomic characterisation
metachronous
sidedness
synchronous
Journal
Molecular and clinical oncology
ISSN: 2049-9469
Titre abrégé: Mol Clin Oncol
Pays: England
ID NLM: 101613422
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
04
01
2021
accepted:
01
07
2021
entrez:
11
10
2021
pubmed:
12
10
2021
medline:
12
10
2021
Statut:
ppublish
Résumé
Metastatic colorectal cancer (mCRC) is a heterogenous disease and its prognosis depends on clinical features, such as tumor sidedness, and whether it is metachronous or synchronous. However, little is known about the overall genomic characterization of mCRC in these clinical subtypes. This single-center observational study included 77 patients with mCRC who underwent somatic and germline exome analysis during the first or second line of therapy in 2018. Somatic and germline variants were determined in addition to tumor mutational burden, ploidy, clonality, human leucocyte antigen typing, neoantigens, and mutational and copy number signatures. Variables associated with sidedness, synchronous status and RAS status were determined using Fisher's test; and variables associated with overall survival were determined using univariate Cox survival models. The present study successfully generated whole exome sequencing analysis in 77 mCRC cases. Among them, 50 were left- and rectal-sided, while 27 were right-sided. Furthermore, 27 were metachronous and 46 were RAS-mutated. The median OS was 3.75 years. It was observed that signature single nucleotide variation (SNV) 26, oncogenic alterations in receptor tyrosine kinase and nucleotide excision repair pathways were associated with tumor sidedness. SNV signature 3, Hedgehog signaling and mismatch repair pathways were associated with synchronous status. Phosphatidylinositol signaling system, ERK signaling and chromatin organization pathways were associated with RAS mutant status. In the whole cohort, metachronous metastasis was associated with improved survival. On gene variation, PTEN, PDGFRA, MYCN and SMAD4 were associated with poor prognosis, as was SNV signature 15. In conclusion, this study highlighted that structural and pathway genomic features are associated with sidedness, synchronous status, RAS status and overall survival and could be helpful to improve the stratification of patients with colorectal cancer.
Identifiants
pubmed: 34631054
doi: 10.3892/mco.2021.2392
pii: MCO-0-0-02392
pmc: PMC8461624
doi:
Types de publication
Journal Article
Langues
eng
Pagination
229Informations de copyright
Copyright: © D'Agay et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
Références
JAMA Oncol. 2017 Feb 01;3(2):211-219
pubmed: 27787550
Nat Med. 2015 Nov;21(11):1350-6
pubmed: 26457759
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
J Clin Oncol. 2015 Mar 1;33(7):692-700
pubmed: 25605843
Clin Cancer Res. 2014 Feb 1;20(3):764-75
pubmed: 24240112
Clin Cancer Res. 2017 Dec 15;23(24):7521-7530
pubmed: 29246904
J Clin Oncol. 2020 Jan 1;38(1):11-19
pubmed: 31725351
Nat Genet. 2018 Sep;50(9):1262-1270
pubmed: 30104763
Genet Med. 2017 Oct;19(10):1105-1117
pubmed: 28492532
JCO Precis Oncol. 2017;2017:
pubmed: 30211344
Genome Med. 2012 Dec 10;4(12):95
pubmed: 23228053
Dig Liver Dis. 2014 Sep;46(9):854-8
pubmed: 24908575
J Clin Oncol. 2007 Apr 20;25(12):1539-44
pubmed: 17442997
Cancer Med. 2020 Feb;9(3):1044-1057
pubmed: 31856410
NPJ Breast Cancer. 2018 Jul 2;4:16
pubmed: 29978035
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Genome Res. 2014 Nov;24(11):1881-93
pubmed: 25060187
Sci Rep. 2020 Feb 17;10(1):2757
pubmed: 32066851
Eur J Cancer. 2018 Nov;103:356-387
pubmed: 30100160
Cell Rep. 2013 Jan 31;3(1):246-59
pubmed: 23318258
Nature. 2012 Jul 18;487(7407):330-7
pubmed: 22810696
Clin Cancer Res. 2019 Mar 15;25(6):1948-1956
pubmed: 30587545
Nat Methods. 2018 Aug;15(8):591-594
pubmed: 30013048
Mediators Inflamm. 2017;2017:4708076
pubmed: 28163397
Ann Oncol. 2009 Nov;20(11):1842-7
pubmed: 19406901
Ann Oncol. 2016 Aug;27(8):1386-422
pubmed: 27380959
Genome Res. 2012 Mar;22(3):568-76
pubmed: 22300766
Genome Med. 2016 Jan 29;8(1):11
pubmed: 26825632
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Cancer Cell. 2018 Jan 8;33(1):125-136.e3
pubmed: 29316426
J Clin Oncol. 2012 Jan 20;30(3):263-7
pubmed: 22162570
Ann Oncol. 2017 Aug 01;28(8):1862-1868
pubmed: 28449055
Nat Commun. 2020 Jul 20;11(1):3644
pubmed: 32686686
Genome Biol. 2016 Feb 22;17:31
pubmed: 26899170