Colon cancer-associated DNA mutations: marker selection for the detection of proximal colon cancer.
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.
Berger
Barry M
BM
Department of dagger Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. bberger@exactsciences.com
Robison
Lauren
L
Glickman
Jonathan
J
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
D004273:DNA, Neoplasm; D005819:Genetic Markers