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World J Gastroenterol. Feb 28, 2014; 20(8): 1940-1950
Published online Feb 28, 2014. doi: 10.3748/wjg.v20.i8.1940
Telomeres, telomerase and colorectal cancer
Roberta Bertorelle, Enrica Rampazzo, Salvatore Pucciarelli, Donato Nitti, Anita De Rossi
Roberta Bertorelle, Enrica Rampazzo, Anita De Rossi, Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, IOV-IRCCS, 35128 Padova, Italy
Salvatore Pucciarelli, Donato Nitti, Department of Surgery, Oncology and Gastroenterology, Section of Surgery, University of Padova, 35128 Padova, Italy
Author contributions: De Rossi A designed the study; all the authors reviewed the literature and analysed the data; De Rossi A and Bertorelle R wrote the article; all authors reviewed and approved the final version of the article.
Supported by A grant from Cariparo, Project “Tumour microenvironment and tumour spread in gastrointestinal cancers”, 2013/2014, No. 6421 to Rampazzo E
Correspondence to: Anita De Rossi, PhD, Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy. anita.derossi@unipd.it
Telephone: + 39-49-8215894 Fax: +39-49-8215894
Received: September 24, 2013
Revised: December 3, 2013
Accepted: January 14, 2014
Published online: February 28, 2014
Processing time: 154 Days and 18.2 Hours
Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and, despite improved treatments, is still an important cause of cancer-related deaths. CRC encompasses a complex of diseases arising from a multi-step process of genetic and epigenetic events. Besides heterogeneity in the molecular and biological features of CRC, chromosomal instability is a hallmark of cancer and cancer cells may also circumvent replicative senescence and acquire the ability to sustain unlimited proliferation. Telomere/telomerase interplay is an important mechanism involved in both genomic stability and cellular replicative potential, and its dysfunction plays a key role in the oncogenetic process. The erosion of telomeres, mainly because of cell proliferation, may be accelerated by specific alterations in the genes involved in CRC, such as APC and MSH2. Although there is general agreement that the shortening of telomeres plays a role in the early steps of CRC carcinogenesis by promoting chromosomal instability, the prognostic role of telomere length in CRC is still under debate. The activation of telomerase reverse transcriptase (TERT), the catalytic component of the telomerase complex, allows cancer cells to grow indefinitely by maintaining the length of the telomeres, thus favouring tumour formation/progression. Several studies indicate that TERT increases with disease progression, and most studies suggest that telomerase is a useful prognostic factor. Plasma TERT mRNA may also be a promising marker for the minimally invasive monitoring of disease progression and response to therapy.

Keywords: Telomere; Telomerase; Telomerase reverse transcriptase; Colorectal cancer; Prognostic marker

Core tip: Telomere/telomerase interplay is an important mechanism involved in both genomic stability and cellular replicative potential. Telomere shortening is an early event that contributes to genetic instability, which plays a key role in the early steps of carcinogenesis. The activation of telomerase, which preserves replicative potential by maintaining the length of telomeres, occurs during the adenoma-carcinoma sequence and increases during tumour progression. While the prognostic value of telomere length is controversial, most studies agree that the level of telomerase in tumours represents a useful prognostic marker. Circulating telomerase reverse transcriptase is a promising marker for the minimally invasive monitoring of disease and response to therapy.