Abstract 1197: Chromosomal aberrations implicated in colorectal adenoma to carcinoma progression as markers of high risk colorectal adenomas.

Abstract

Abstract Background: Advanced adenomas are considered as an important intermediate endpoint for colorectal cancer (CRC) screening. Still the majority of these lesions do not progress to cancer. Hence, using this intermediate endpoint in evaluation of screening programs may lead to an overestimation of the effect of screening. Underlying genomic alterations like chromosomal instability characteristic of colorectal adenoma to carcinoma progression (gains of 8q, 13q, 20q and losses of 8p 15q, 18q) may more precisely mark high risk adenomas. Previously, we have shown that the presence of two or more of these particular chromosomal alterations was associated with malignant progression. The aim of this study is to evaluate the prevalence of chromosomal aberrations implicated in colorectal adenoma to carcinoma progression in advanced and non-advanced colorectal adenomas. Methods: The prevalence of DNA copy number gains and losses of 8q, 13q, 15q, 18q, 20q, 8p and 17p was determined in 65 advanced and 58 non-advanced adenomas using multiplex ligation-dependent probe amplification (MLPA). Adenomas ≥1.0 cm, with any villous features (i.e. tubulovillous or villous adenoma) or high-grade dysplasia were called advanced adenomas, while tubular adenomas, <1.0 cm and with low-grade dysplasia were called non-advanced adenomas. Results: 22% of advanced adenomas showed two or more cancer associated chromosomal aberrations compared to 2% in the non-advanced adenomas. DNA copy number gain of 20q was the most frequent chromosomal aberration found in 12.2 % of the adenomas. DNA copy number gains occurred more frequently than losses. Presence of 13q and 20q gains were significantly more present in adenomas >1.0 cm than <1.0 cm (p=0.01 and p=0.001 respectively). 8q gain and 17p loss were significantly more present in adenomas with high degree dysplasia than with low degree dysplasia (p=0.04 and p=0.01 respectively). None of the DNA copy number changes studied was associated with the histological subtypes of advanced adenomas. Conclusions: 22% of the advanced adenomas and 2% of the non-advanced adenomas showed two or more CRC associated chromosomal aberrations. These findings are consistent with the hypothesis that the morphological parameters used to classify adenomas lack specificity as an intermediate endpoint in CRC screening. Citation Format: Begoña Diosdado, Jochim S. Terhaar sive Droste, Anne S. Bolijn, Myrthe K. van Burink, Nicole CT van Grieken, Beatriz Carvalho, Chris J. Mulder, Gerrit A. Meijer. Chromosomal aberrations implicated in colorectal adenoma to carcinoma progression as markers of high risk colorectal adenomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1197. doi:10.1158/1538-7445.AM2013-1197