A retrospective case control study (n=119) compared left-sided biopsies from surveillance colonoscopies of IBD patients who progressed to cancer 1-5 years later with matched controls by means of low-pass whole genome sequencing [1]. This technique is able to detect chromosomal copy number alterations (CNAs), which are associated with colorectal carcinogenesis. All evaluated biopsies were free of dysplasia or colorectal cancer. Dr Ibrahim Al Bakir (Queen Mary University of London, UK) presented the findings of the study.
Both cases (81.8%) and controls (76.2%) showed CNAs in at least 1 of the 4 biopsies that were assessed. However, case biopsies had significantly higher proportions of genome-bearing CNAs, a greater number of CNAs, and a greater mean size of CNAs, compared with control subjects. In addition, larger reductions of CNAs were almost exclusively observed in cases (P<0.05). The risk prediction of dysplasia or colorectal cancer by detection of large CNA reductions in any biopsy was analysed by Kaplan-Meier and ROC analysis. The results demonstrated a specificity of 96% and a sensitivity of 26%, with an accuracy of 73%.
Dr Al Bakir argued that low-pass whole genome sequencing is mostly feasible for high-risk patients, due to the high specificity and low sensitivity of the technique. However, fine-tuning of the technique could improve its accuracy. For example, the current study found that CNAs occur more frequently in the rectum than in the sigmoid colon or descending colon (P<0.001). Dr Al Bakir therefore mentioned that it could be interesting to evaluate rectum biopsies only in future studies.
- Al Bakir I, et al. Developing a Cost-Effective Genomic Biomarker of Cancer Risk in Patients with Ulcerative Colitis using Low-Pass Whole Genome Sequencing of Unselected Endoscopic Biopsies: A Case-Control Study. OP38, ECCO 2021 Virtual Congress, 2-3 & 8-10 July.
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Table of Contents: ECCO 2021
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