title: Colon cancer-associated DNA mutations: marker selection for the detection of proximal colon cancer.
abstract: This study evaluates the potential ability of a specific panel of DNA mutations to identify right-sided colorectal carcinomas (CRCs) that would be missed by a flexible sigmoidoscopy (FS) screening program. This panel could then be applied to stool DNA analysis for noninvasive proximal CRC detection. A series of resected right-sided CRCs from 101 patients who had no left-sided advanced colonic neoplasms distal to the splenic flexure were analyzed. Tumor DNA was isolated from microdissected tumor sections. Deletions in the BAT-26 locus, a marker of microsatellite instability, and mutations at 19 loci spread among the p53, K-ras, and Apc genes were detected following PCR amplification. Mutations were identified in 83% of successfully amplified samples and were variably present in each of the target sites: p53 (42%), Apc (37%), K-ras (28%), and BAT-26 (24%). Mutations were identified across all Dukes stages (CIS/A 6/8 [75%], B 41/51[80%], C 30/32 (94%), and D 6/9 [67%]). Our data suggest that this 20-marker mutation panel may be associated with more than 80% of cancers undetectable by FS. The adjunctive use of stool DNA mutation analysis using this marker panel in FS CRC screening programs may significantly increase the detection of proximal CRC.
authors.affiliation: Department of dagger Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. bberger@exactsciences.com
authors.forename: Barry M
authors.initials: BM
authors.lastname: Berger
authors.forename: Lauren
authors.initials: L
authors.lastname: Robison
authors.forename: Jonathan
authors.initials: J
authors.lastname: Glickman
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005243:Feces / Q000737:chemistry; D005260:Female; D017491:Genes, APC / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D012812:Sigmoidoscopy
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers