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Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):2992-3000. doi: 10.1016/j.bbadis.2018.06.010. Epub 2018 Jun 14.

Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response.

Author information

1
Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain.
2
Hereditary Cancer Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERONC, L'Hospitalet de Llobregat, Barcelona, Spain.
3
Department of Pathology, University Hospital Bellvitge (HUB-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
4
Digestive Service, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, Spain.
5
Department of Gastroenterology, University Hospital Bellvitge (HUB-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
6
Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: rebecasanz@iconcologia.net.
7
Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. Electronic address: v.moreno@iconcologia.net.

Abstract

Telomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent genetic alterations in malignant transformation. Here we aim to estimate telomere length from whole-exome sequencing data in colon tumors and normal colonic mucosa, and to analyze the potential association of telomere length with clinical factors and gene expression in colon cancer. Reads containing at least five repetitions of the telomere sequence (TTAGGG) were extracted from the raw sequences of 42 adjacent normal-tumor paired samples. The number of reads from the tumor sample was normalized to build the Tumor Telomere Length Ratio (TTLR), considered an estimation of telomere length change in the tumor compared to the paired normal tissue. We evaluated the associations between TTLR and clinical factors, gene expression and copy number (CN) aberrations measured in the same tumor samples. Colon tumors showed significantly shorter telomeres than their paired normal samples. No significant association was observed between TTLR and gender, age, tumor location, prognosis, stromal infiltration or molecular subtypes. The functional gene set enrichment analysis showed pathways related to immune response significantly associated with TLLR. By extracting a relative measure of telomere length from whole-exome sequencing data, we have assessed that colon tumor cells predominantly shorten telomeres, and this alteration is associated with expression changes in genes related to immune response and inflammation in tumor cells.

KEYWORDS:

Colon cancer; Exome sequencing; Immune response; Telomere length

PMID:
29908233
DOI:
10.1016/j.bbadis.2018.06.010
[Indexed for MEDLINE]
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