BACKGROUND AND OBJECTIVE: Current surveillance strategies for colorectal cancer following polypectomy are determined by endoscopic and histopathological factors. Such a distinction has been challenged. The present study was designed to identify molecular parameters in colonic polyps potentially defining new sub-groups at risk. METHODS: One hundred patients were enrolled in this multicentre study. Polyps biopsies underwent formalin-free processing (PAXgene, PreAnalytiX) and targeted next generation sequencing (38 genes (QIAGEN), NextSeq 500 platform (Illumina)). Genetic and histopathological analyses were done blinded to other data. RESULTS: In 100 patients, 224 polyps were removed. Significant associations of genetic alterations with endoscopic or histological polyp characteristics were observed for BRAF, KRAS, TCF7L2, FBXW7 and CTNNB1 mutations. Multivariate analysis revealed that polyps ≥ 10 mm have a significant higher relative risk for harbouring oncogene mutations (relative risk 3.467 (1.742-6.933)). Adenomas and right-sided polyps are independent risk factors for CTNNB1 mutations (relative risk 18.559 (2.371-145.245) and 12.987 (1.637-100.00)). CONCLUSIONS: Assessment of the mutational landscape of polyps can be integrated in the workflow of current colonoscopy practice. There are distinct genetic patterns related to polyp size and location. These results suffice to optimise individual risk calculation and may help to better define surveillance intervals.
BACKGROUND AND OBJECTIVE: Current surveillance strategies for colorectal cancer following polypectomy are determined by endoscopic and histopathological factors. Such a distinction has been challenged. The present study was designed to identify molecular parameters in colonic polyps potentially defining new sub-groups at risk. METHODS: One hundred patients were enrolled in this multicentre study. Polyps biopsies underwent formalin-free processing (PAXgene, PreAnalytiX) and targeted next generation sequencing (38 genes (QIAGEN), NextSeq 500 platform (Illumina)). Genetic and histopathological analyses were done blinded to other data. RESULTS: In 100 patients, 224 polyps were removed. Significant associations of genetic alterations with endoscopic or histological polyp characteristics were observed for BRAF, KRAS, TCF7L2, FBXW7 and CTNNB1 mutations. Multivariate analysis revealed that polyps ≥ 10 mm have a significant higher relative risk for harbouring oncogene mutations (relative risk 3.467 (1.742-6.933)). Adenomas and right-sided polyps are independent risk factors for CTNNB1 mutations (relative risk 18.559 (2.371-145.245) and 12.987 (1.637-100.00)). CONCLUSIONS: Assessment of the mutational landscape of polyps can be integrated in the workflow of current colonoscopy practice. There are distinct genetic patterns related to polyp size and location. These results suffice to optimise individual risk calculation and may help to better define surveillance intervals.
Authors: Douglas K Rex; Dennis J Ahnen; John A Baron; Kenneth P Batts; Carol A Burke; Randall W Burt; John R Goldblum; José G Guillem; Charles J Kahi; Matthew F Kalady; Michael J O'Brien; Robert D Odze; Shuji Ogino; Susan Parry; Dale C Snover; Emina Emilia Torlakovic; Paul E Wise; Joanne Young; James Church Journal: Am J Gastroenterol Date: 2012-06-19 Impact factor: 10.864
Authors: C De Filippo; C Luceri; G Caderni; M Pacini; L Messerini; A Biggeri; E Mini; F Tonelli; F Cianchi; P Dolara Journal: Scand J Gastroenterol Date: 2002-09 Impact factor: 2.423
Authors: Vanessa L Hale; Jun Chen; Stephen Johnson; Sean C Harrington; Tracy C Yab; Thomas C Smyrk; Heidi Nelson; Lisa A Boardman; Brooke R Druliner; Theodore R Levin; Douglas K Rex; Dennis J Ahnen; Peter Lance; David A Ahlquist; Nicholas Chia Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-09-26 Impact factor: 4.254
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Hashem A Shihab; Julian Gough; David N Cooper; Peter D Stenson; Gary L A Barker; Keith J Edwards; Ian N M Day; Tom R Gaunt Journal: Hum Mutat Date: 2012-11-02 Impact factor: 4.878
Authors: Jon A Lorentzen; Krzysztof Grzyb; Paula M De Angelis; Geir Hoff; Tor J Eide; Per Arne Andresen Journal: Clin Med Insights Pathol Date: 2016-09-07