Mutations at the APC exon 15 in the colorectal neoplastic tissues of serial array.
Although the APC protein is known to participate in cellular proliferation and apoptosis, APC mutations have been thought to play a major role in the early stage of colorectal tumorigenesis. The somatic APC mutation of exon 15 was assessed to determine its impact on various stages of colorectal tumorigenesis. The colorectal neoplastic tissues of serial array studied included sporadic adenomas (group 1, n = 36), adenomas (group 2, n = 33), and carcinomas (group 3, n = 32) in the synchronous adenoma and carcinoma as well as sporadic carcinomas (group 4, n = 36). Aberrant DNA was detected by protein truncation test and confirmed by direct sequencing. The mutation prevalence was 36.1% in group 1, 45.5% in group 2, 59.4% in group 3, and 41.7% in group 4 with no differences among the groups. Among the 18 patients with synchronous adenoma and carcinoma, 9 had mutation in their adenomas and 12 in their carcinomas. The mutation loci and patterns did not differ in adenomas and carcinomas. Mutations in the mutation cluster region (MCR) were much more frequent than in the preceding region of MCR, i.e., 85.7% vs. 14.3%. The mutation prevalence of villous adenomas appeared greater than that of tubular adenoma (3/21 vs. 3/4). Predominant pathogenic mutations at MCR suggest that the APC mutation is implicated in all stages of colorectal tumorigenesis.
Kim
J C
JC
Department of Surgery, University of Ulsan College of Medicine and Asan Institute for Life Sciences, 388-1 Poongnap-Dong, Songpa-Ku, Seoul 138-736, Korea. jckim@www.amc.seoul.kr
Koo
K H
KH
Lee
D H
DH
Roh
S A
SA
Kim
H C
HC
Yu
C S
CS
Kang
G H
GH
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D046508:Culture Techniques; D005091:Exons / Q000235:genetics; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D016133:Polymerase Chain Reaction; D012044:Regression Analysis; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D005819:Genetic Markers