Abstract 1470: Relative telomere length in tumor tissue and adjacent mucosa of colorectal cancer patients

Abstract

Abstract Colorectal cancer (CRC) represents a major public health problem, being the fourth leading cause of cancer related deaths mainly due to the late diagnosis and a lack of proper prognostic markers. According to the current knowledge, shortening of telomeres is important contributor in cancer onset. Telomeres, repetitive TTAGGG sequences and boud proteins, are structures at the end of all linear eukaryotic chromosomes. Telomeres are double-edged sword regarding to cancer. On one hand, they serve as a potent tumor-supressor mechanism limiting the cells ability of uncontroled growth. However, on the other hand, shortening of telomeres can lead to the formation of anaphase bridges, initiation of breakage-fusion-bridges cycles and eventually to the induction of chromosome instability phenotype. Telomeric regions are composed of microsatellite repeats and DNA mismatch repair (MMR) defects should directly affect telomere length. Studies looking into the relationship between microsatellite instability (MSI) and telomere length have been sparse. We hypothesize that CRC patients with MSI should have better prognosis, longer survival, also due to the MMR defects in telomere regions replication failure. The aim of our present study was to investigate relative telomere length (RTL) in tumor tissue and adjacent mucosa of 650 CRC patients; it is the largest study on RTL in target tissue so far. Moreover, we measured RTL in peripheral blood lymphocytes obtained from 150 cancer patients. Tumor and adjacent non-affected tissue samples were obtained from patients at surgical resection. RTL was measured using monochrome multiplex quantitative PCR method. Despite the analysis is still running, our preliminary results showed significantly shorter RTL in tumor tissues as compared to adjacent mucosa. The shortest RTL was discovered in right, ascendent part of colon (0.68±0.59, 25.5% of cases), followed by left, descendent colon (0.77±0.47, 37.6%) and the longest RTL was in rectal tumors (0.92±0.69, 36.9%). We recorded gradually increasing RTL ratio (RTL in tumor tissue/ RTL in adjacent mucosa) in later stages according to TNM staging system. Interestingly, patients with RTL ratio > 1 had also worse survival. RTL of CRC tissue and adjacent mucosa may provide a valuable prognostic tool in patients treatment management. This study was supported by GACR 15-14789S and by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic Citation Format: Michal Kroupa, Vaclav Liska, Krishna Rachakonda, Marketa Urbanova, Michaela Schneiderova, Katerina Jiraskova, Ondrej Vycital, Ludmila Vodickova, Rajiv Kumar, Pavel Vodicka. Relative telomere length in tumor tissue and adjacent mucosa of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1470.