Genetic and epigenetic changes in the APC gene in sporadic colorectal carcinoma with synchronous adenoma.
OBJECTIVE
Somatic APC mutation, frequently associated with colorectal tumors, is implicated in the early stage of tumorigenesis. This study was performed to identify APC-related colorectal tumorigenesis in sporadic colorectal carcinomas with synchronous adenoma.


METHODS
We screened the entire coding region of APC and also assessed 5q LOH, 5q MSI, and promoter hypermethylation in fresh colorectal tissue and the lymphocytes of 31 patients with synchronous colorectal adenoma and carcinoma.


RESULTS
The APC mutation prevalence was greater in carcinomas (70%) than in adenomas (45%). The 5q LOH and MSI were identified in 7 and in 5 of 31 carcinomas and in 6 each of 43 adenomas, respectively. The APC promoter methylation was identified in 3 cases each of both carcinomas and adenomas. Mutations in cases with 5q LOH were identified exclusively from codons 959 to the 3' end of exon 15. Otherwise mutations identified between exons 1 and 14 showed additional mutation on exon 15 and no additional mutation in two cases. All carcinomas with 5q LOH, 5q MSI, or methylation included at least one APC mutation, whereas 5 carcinomas and 6 adenomas showed solely an APC mutation. Both alleles were disrupted in 1 of 31 normal mucosa (3.2%), 12 of 40 adenomas (30%), and 18 of 33 carcinomas (54.5%).


CONCLUSIONS
Genetic and epigenetic events encompassing APC occur variously among patients and tissues in sporadic colorectal cancer patients with synchronous colorectal adenoma. Moreover, these changes sometimes appear to be accumulated in all of the stages of colorectal tumorigenesis.
Kim
Jin 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@amc.seoul.kr
Koo
Kum H
KH
Roh
Seon A
SA
Cho
Yong K
YK
Kim
Hee C
HC
Yu
Chang S
CS
Kim
Ho J
HJ
Kim
Jung S
JS
Cho
Moon K
MK
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002895:Chromosomes, Human, Pair 5; D018389:Codon, Nonsense / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D017353:Gene Deletion; D017491:Genes, APC; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000378:metabolism; D018895:Microsatellite Repeats; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D015995:Prevalence; D011401:Promoter Regions, Genetic
D018389:Codon, Nonsense