{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:10:00Z","timestamp":1768569000695,"version":"3.49.0"},"posted":{"date-parts":[[2024,7,8]]},"group-title":"Gastroenterology","reference-count":44,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), and this risk increases dramatically in those who develop low-grade dysplasia (LGD). However, there is currently no accurate way to risk-stratify patients with LGD, leading to both over- and under-treatment of cancer risk. Here we show that the burden of somatic copy number alterations (CNAs) within resected LGD lesions strongly predicts future cancer development. We performed a retrospective multi-centre validated case-control study of n=122 patients (40 progressors, 82 non-progressors, 270 LGD regions). Low coverage whole genome sequencing revealed CNA burden was significantly higher in progressors than non-progressors (p=2x10\n                  <jats:sup>-6<\/jats:sup>\n                  in discovery cohort) and was a very significant predictor of CRC risk in univariate analysis (odds ratio = 36; p=9x10\n                  <jats:sup>-7<\/jats:sup>\n                  ), outperforming existing clinical risk factors such as lesion size, shape and focality. Optimal risk prediction was achieved with a multivariate model combining CNA burden with the known clinical risk factor of incomplete LGD resection. The measurement of CNAs in LGD lesions is a robust, low-cost and rapidly translatable predictor of CRC risk in IBD that can be used to direct management and so prevent CRC in high-risk individuals whilst sparing those at low-risk from unnecessary intervention.\n                <\/jats:p>","DOI":"10.1101\/2024.07.08.24309811","type":"posted-content","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T19:10:13Z","timestamp":1720465813000},"source":"Crossref","is-referenced-by-count":0,"title":["Low coverage whole genome sequencing of low-grade dysplasia strongly predicts colorectal cancer risk in ulcerative colitis"],"prefix":"10.64898","author":[{"given":"Ibrahim 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