Involvement of APC and K-ras mutation in non-polypoid colorectal tumorigenesis.
The aim of this study was to clarify the role of APC and K-ras mutations in non-polypoid colorectal tumorigenesis. DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 submucosally invasive carcinomas (47 polypoid, 19 non-polypoid) and 34 advanced carcinomas were examined for K-ras codon 12 point mutations and APC mutations in the mutation cluster region. K-ras mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs 31%: P= 0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs 56%: P = 0.0008), and was relatively low compared with that in polypoid adenomas (11% vs 31%). APC mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs 43%: P = 0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. Polypoid adenomas, polypoid carcinomas and advanced carcinomas had almost the same frequency. There may be some pathway other than the conventional adenoma-carcinoma sequence in development of non-polypoid carcinomas. The precursors of most non-polypoid carcinomas are considered to be de novo or superficial depressed adenomas. In this non-polypoid pathway, APC mutation seems to be requisite but K-ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas.
Umetani
N
N
Department of Surgical Oncology, School of Medicine, The University of Tokyo, Japan.
Sasaki
S
S
Masaki
T
T
Watanabe
T
T
Matsuda
K
K
Muto
T
T
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D018256:Adenomatous Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D016368:Frameshift Mutation / Q000235:genetics*; D017491:Genes, APC / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D009367:Neoplasm Staging; D017354:Point Mutation / Q000235:genetics*