Abstract 2316: Malignant Potential of Colorectal Adenoma Based on the Telomere Length

Abstract Telomere attrition is a well-known hallmark of malignancy in cancer tissue. Our study analyzed the relative telomere length in adenomas, precursor lesions of colorectal adenocarcinoma. We investigated if the accelerated telomere length shortening occurs before potential malignant transformation to adenocarcinoma and corresponds with clinicopathological characteristics. Relative telomere length was measured in 145 patients using multiplex qPCR. We have recorded significant shortening of telomeres in the adenoma tissue compared to adjacent mucosa (Wilcoxon Signed Rank test, p < 0.0001). Further, we have observed a weak inverse relationship between both adenoma and mucosa telomere length and age (Spearman's and Pearson's correlation, p = 0.021 and p = 0.027, respectively), contrary to our previous study of colorectal cancer patients (n = 696), where the inverse correlation of telomere length was detected only in the non-malignant mucosa (Pearson's correlation, p = 0.029). However, the telomere length ratio of adenoma to adjacent mucosa did not correspond with the degree of dysplasia according to the Vienna classification (Kruskal-Wallis test, p = 0.572). Also, there was no difference in the telomere length ratio among histological types of adenomas and no association with the adenoma localization in proximal and distal colon or rectum (Kruskal-Wallis test, p = 0.648 and p = 0.459, respectively). Preliminary results indicate that telomere shortening occurs indeed as early as in a stage of adenomatous polyps, and it is less pronounced in adenomas compared to cancerous cells. However, the relative telomere length does not seem to correspond with adenoma progression towards malignancy. In planned experiments, we intend to assess mitochondrial DNA damage caused by 8-oxoguanine DNA adducts. These major oxidative base lesions can arise from endogenous reactive oxygen species and impact, among other things, the integrity of telomeres through double-strand breaks to DNA. Mitochondrial DNA is more prone to accumulation of oxidative damage than nuclear DNA and thus might be useful as an early, additional indicator of the precancerous character of adenoma. The study will reveal whether increased mitochondrial DNA damage and telomere loss are commonly present and linked together in adenomas. This study was supported by the Charles University (project GA UK No. 120, UNCE/MED/006) and the Grant Agency of the Czech Republic (21-04607X, 21-27902S). Citation Format: Kristyna Tomasova, Michal Kroupa, Anna Siskova, Josef Horak, Ondrej Vycital, Vaclav Liska, Ludmila Vodickova, Pavel Vodicka. Malignant potential of colorectal adenoma based on the telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2316.