Clonal evolution of colorectal cancer in IBD.
Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.
Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.|Inflammatory Bowel Disease Unit, Level 4 St Mark's Hospital, Watford Road, London HA1 3UJ, UK.
Chang-Ho R
CR
Choi
Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.|Inflammatory Bowel Disease Unit, Level 4 St Mark's Hospital, Watford Road, London HA1 3UJ, UK.
Ibrahim Al
IA
Bakir
Inflammatory Bowel Disease Unit, Level 4 St Mark's Hospital, Watford Road, London HA1 3UJ, UK.
Ailsa L
AL
Hart
Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Trevor A
TA
Graham
D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications*
D014408:Biomarkers, Tumor