Reduced Telomere Length in Colorectal Carcinomas

Tong-Bao Feng,Lei-Ming Cai,Chun-Jian Qi,Ke-Qing Qian

doi:10.7314/apjcp.2012.13.2.443

Tong-Bao Feng, Lei-Ming Cai + Show 2 more

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https://doi.org/10.7314/apjcp.2012.13.2.443

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Abstract

Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. The aim of this study was to determine whether telomere length is associated with the colorectal carcinoma. A total of 148 colorectal cancer (CRC) samples and corresponding adjacent non-cancerous tissues were evaluated for telomere length, P53 mutation, and cyclooxygenase-2 (COX-2) mutation detected by fluorescent immunohistochemistry. Telomere length was estimated by real-time PCR. Samples with a T/S>1.0 have an average telomere length greater than that of the standard DNA; samples with a T/S<1.0 have an average telomere length shorter than that of the standard DNA. Telomeres were shorter in CRCs than in adjacent tissues, regardless of tumor stage and grade, site, or genetic alterations (P=0.004). Telomere length in CRCs also had differences with COX-2 status (P=0.004), but did not differ with P53 status (P=0.101), tumor progression (P=0.244), gender (P=0.542), and metastasis (0.488). There was no clear trend between T/S optimal cut-off values (<1 or > 1) and colorectal tumor progression, metastasis, gender, P53 and COX-2 status. These findings suggesting that telomere shortening is associated with colorectal carcinogenesis but does not differ with tumor progression, gender, and metastasis.

Highlights

Telomeres are non-coding tandem repetitive DNA sequences (TTAGGG) at the end of chromosomes, and play important roles in maintaining genomic integrity and stability (Verdun et al, 2007)
In 45 colorectal carcinoma samples, telomere length was determined by real-time PCR, containing 27 length greater than that of the standard DNA; samples with a telomere/ single copy-gene ratio (T/S)
In this study we demonstrated telomere length in colorectal cancer was shorter than in adjacent carcinoma

Summary

Introduction

Telomeres are non-coding tandem repetitive DNA sequences (TTAGGG) at the end of chromosomes, and play important roles in maintaining genomic integrity and stability (Verdun et al, 2007). Colorectal carcinomas (CRCs) comprise a heterogeneous complex of diseases differing in molecular pathways and biological characteristics, arising through a multi-step carcinogenic process. These events generally follow exposure to carcinogens and result in the selection of clonal cells with uncontrolled growth (d’Adda di Fagagna et al, 2003).The earliest events are mutations, deletions or polysomy at genomic level, but these changes do not always lead to changes in cell morphology or tissue structure (Greider et al.,1989; Gorgoulis et al, 2005). CRCs cells acquire the hallmarks of cancer during this carcinogenic selection process (Meeker et al, 2004). There are contradictory reports about the independent prognostic value of telomere length determination

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