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Br J Cancer. 2017 Jul 25;117(3):421-431. doi: 10.1038/bjc.2017.208. Epub 2017 Jul 6.

Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component.

Author information

1
Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), CIBERESP, Gran Via 199, Hospitalet Llobregat, 08908 Barcelona, Spain.
2
Molecular Mechanisms and Experimental Therapy Cancer Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
3
Gastroenterology Service, Hospital de Viladecans, Barcelona, Spain.
4
Faculty of Medicine, Department of Clinical Sciences, University of Barcelona (UB), Barcelona, Spain.
5
Department of General and Digestive Surgery, Bellvitge University Hospital, Barcelona, Spain.
6
Hereditary Cancer Program, Catalan Institute of Oncology (ICO) and CIBERONC, Barcelona, Spain.
7
Oncology Department, Catalan Institute of Oncology (ICO) and CIBERONC, Barcelona, Spain.

Abstract

BACKGROUND:

Somatic copy number aberrations (CNAs) are common acquired changes in cancer cells having an important role in the progression of colon cancer (colorectal cancer, CRC). This study aimed to perform a characterisation of CNA and their impact in gene expression.

METHODS:

Copy number aberrations were inferred from SNP array data in a series of 99 CRC. Copy number aberration events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes. All analyses were adjusted for the quantity of stroma in each sample, which was inferred from gene expression data.

RESULTS:

High heterogeneity among samples was observed; the proportion of altered genome ranged between 0.04 and 26.6%. Recurrent CNA regions with gains were frequent in chromosomes 7p, 8q, 13q, and 20, whereas 8p, 17p, and 18 cumulated losses. A significant positive correlation was observed between the number of somatic mutations and total CNA (Spearman's r=0.42, P=0.006). Approximately 37% of genes located in CNA regions changed their level of expression and the average partial correlation (adjusted for stromal content) with copy number was 0.54 (interquartile range 0.20 to 0.81). Altered genes showed enrichment in pathways relevant for CRC. Tumours classified as CMS2 and CMS4 by the consensus molecular subtyping showed higher frequency of CNA. Losses of one small region in 1p36.33, with gene CDK11B, were associated with poor prognosis. More than 66% of the recurrent CNA were validated in the The Cancer Genome Atlas (TCGA) data when analysed with the same procedure. Furthermore, 79% of the genes with altered expression in our data were validated in the TCGA.

CONCLUSIONS:

Although CNA are frequent events in microsatellite stable CRC, few focal recurrent regions were found. These aberrations have strong effects on gene expression and contribute to deregulate relevant cancer pathways. Owing to the diploid nature of stromal cells, it is important to consider the purity of tumour samples to accurately calculate CNA events in CRC.

PMID:
28683472
PMCID:
PMC5537504
DOI:
10.1038/bjc.2017.208
[Indexed for MEDLINE]
Free PMC Article

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