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Longitudinal molecular characterization of endoscopic specimens from colorectal lesions

World Journal of Gastroenterology 2016年第20期22卷 4936-4945页

作者： Petra Minarikova lucie benesova Tereza Halkova Barbora Belsanova Stepan Suchanek Jiri Cyrany Inna Tuckova Jan Bures Miroslav Zavoral Marek Minarik Department of Internal Medicine 1st Faculty of Medicine of Charles University and Military University Hospital Genomac Research Institute Centre for Applied Genomics of Solid Tumors 2nd Department of Internal Medicine - Gastroenterology Charles University Faculty of Medicine at Hradec Kralove University Teaching Hospital

AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice. METHODS: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of Cp G-islandmethylator phenotype(CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC ***: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF + type with proximal location. CONCLUSION: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated(methylation) pathway.

关键词： Colorectal cancer Cp G-island methylator phenotype DNA Microsatellite instability BRAF

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