Abstract 716: Genomic classification of longitudinally observed small colorectal polyps
Authors: Meta C. van Lanschot, Beatriz Carvalho, Charlotte J. Tutein Nolthenius, Christian R. Rausch, Ernst J. Kuipers, Jaap Stoker, Evelien Dekker, Gerrit A. Meijer
Journal: Cancer Research (2017)

Abstract Introduction: Colorectal polyps are very common in elderly people with a prevalence of 15-30% reported in screening series. However, only a minority of 5% of these lesions is estimated to develop into invasive cancers, whereas others will remain stable or regress over time. In standard practice all polyps observed during colonoscopy are removed by polypectomy and therefore, knowledge about their natural history is limited. In this study, small (6-9mm) colorectal polyps were followed over time and subsequently resected during colonoscopy. Aim: The prevalence of DNA copy number alterations (CNAs), a feature associated with adenoma to carcinoma progression, was compared in polyps that morphologically progressed versus those that did not. Methods: In the CT-colonography (CTC) arm of the COCOS-trial1 small 6-9mm polyps were left in situ. After a three-year surveillance interval, growth according to CTC of 95 small polyps was measured. Based on overall volumetric change on CTC, polyps were classified as either progressed (&amp;gt;30% growth), stable (30% to -30% growth) or regressed (&amp;lt;-30% growth). From 65 resected polyps, formalin-fixed paraffin-embedded material was retrieved and reviewed by an expert pathologist (GAM). Of these polyps, 48% (31/65) progressed, 41% (27/65) remained stable and 11% (7/65) regressed. Seventy-two percent (47/65) were tubular adenomas, 14% (9/65) tubulovillous adenomas, 3% (2/65) sessile serrated lesions and 11% (7/65) hyperplastic polyps. Subsequently, the samples that yielded sufficient quality DNA were analyzed with low-coverage whole genome sequencing (HiSeq, Illumina, San Diego, CA, USA). DNA copy number status was called with the R-package QDNAseq. Results: From 50/68 resected polyps, originating from 38 individuals (mean age of 66.8 years (s.d. 7.0); 63% male), sufficient DNA was available. The mean surveillance interval of these polyps was 3.27 years (s.d. 0.29). The mean number of CNAs per sample was 0.8 (range 0-8), the most frequently observed was 13q gain (20%). No significant differences in number, or regions of CNAs were observed between polyps that progressed and the ones that did not change or diminished in size (stable or regressed). Larger polyps showed more CNAs, of which specifically 13q gain was more often present (43% in ≥10mm and 8% in &amp;lt;10mm polyps). Of note, no serrated lesions were ≥10mm. No differences in CNAs were found between the different histological subtypes. Conclusions: In a series of colorectal polyps left in situ for an average 3.27 years, no difference in prevalence of DNA copy number alterations was observed between polyps that volumetrically progressed and those that did not. Of the CNAs observed, 13q gain was most prevalent and found in 43% of the ≥10mm polyps. 1. Stoop, E. M. et al. Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: A randomised controlled trial. Lancet Oncol. 13, 55-64 (2012). Citation Format: Meta C. van Lanschot, Beatriz Carvalho, Charlotte J. Tutein Nolthenius, Christian R. Rausch, Ernst J. Kuipers, Jaap Stoker, Evelien Dekker, Gerrit A. Meijer. Genomic classification of longitudinally observed small colorectal polyps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 716. doi:10.1158/1538-7445.AM2017-716