Nagase, H., Miyoshi, Y., Horii, A., Aoki, T., Ogawa, M. & Utsunomiya, J. et al. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res. 52, 4055-4057 (original) (raw)
Related papers
Cancer research, 1992
Recently we have isolated the adenomatous polyposis coli (APC) gene which causes familial adenomatous polyposis (FAP), and its germ-line mutations in a substantial number of FAP patients have been identified. On the basis of this information, we compared the location of germ-line mutations in the APC gene in 22 unrelated patients (12 of whom have been reported previously) with the number of colorectal polyps developed in FAP patients; 17 were sparse types and five were profuse types. All but one of the mutations were considered to cause truncation of the gene product by frame-shift due to deletion (14 cases) or nonsense mutation (seven cases). The location of the germ-line mutations seems to correlate with the two clinical types; germ-line mutations in five FAP patients with profuse polyps were observed between codon 1250 and codon 1464, whereas mutations in 17 FAP patients with fewer polyps were observed in the other regions of the APC gene. The result suggests that the number of c...
Human Mutation, 2001
Germline mutations in the tumor-suppresor APC gene are associated with hereditary familial adenomatous polyposis (FAP) and somatic mutations are common in sporadic colorectal cancer. In this study, we report the identification of three novel germline mutations: 1682-1683insA, 3252-3253insAT, 3544A>T and a new somatic mutation 4130-4131delTT, all giving rise to truncated APC proteins. The majority of the mutations we found originate a truncated APC protein and cause the FAP phenotype. However, special attention must be given to the missense mutations Asp1822Val and Ser2621Cys since their segregation with the FAP phenotype is questionable. In our FAP families we did not find any genetical alterations at codon 1309, being this mutation the most frequent reported in APC. Differences in the recurrence of pathological mutations in APC could exist among populations. However, epidemiological studies must be performed to confirm this hypothesis. Hum Mutat 18:355, 2001. © 2001 Wiley-Liss, Inc.
APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis
British Journal of Cancer - BRIT J CANCER, 2000
Correlations between germline APC mutation sites and colorectal pathophenotypes, as evaluated by the direct count of adenomas at colectomy, were investigated analysing colectomy specimens from 29 FAP patients carrying one mis-sense (codon 208) and 14 frame-shift or non-sense APC mutations (codons 232, 367, 437, 623, 876, 995, 1061, 1068, 1075, 1112, 1114, 1309, 1324, 1556). The mis-sense mutation at codon 208 was associated with a relatively mild colorectal pathophenotype. The mutation at codon 367, subject to alternative splicing, was associated with attenuated FAP. The mutation at codon 1309 was associated with the profuse colorectal adenomatosis. For 13 mutations, predicted to result in null alleles or truncated APC proteins, we correlated density and distribution of colorectal adenomas with the predicted functional effects of the mutation. The most severe colorectal pathophenotype was significantly associated with the truncating mutation at codon 1309, which is located downstrea...
Association of APC gene mutations and histological characteristics of colorectal adenomas
PubMed, 1994
Fifty-nine colonic adenomas and 6 hyperplastic colonic polyps were analyzed by single-strand conformation polymorphism analysis for mutations in the adenomatous polyposis coli gene (APC). Frameshifts and premature stop codons in at least one copy of APC were detected in 25 of these adenomas. Five adenomas carried 2 APC mutations. No mutations in APC were found in any of the 6 hyperplastic polyps. The detection of APC mutations increased with size and degree of dysplasia and in rectal as compared to colonic adenomas, although the association was not statistically significant. The frequency of detectable APC mutations was higher in tubulovillous and villous adenomas (10 of 13) than in tubular adenomas (15 of 45) (odds ratio, 6.67; 95% confidence limits, 1.39-41.83; P = 0.005). The significance of the association between the detection of APC mutations and a villous architecture was confirmed in multivariate analysis (relative risk, 6.67; 95% confidence limits, 1.54-28.8; P = 0.005). In conclusion, APC mutation plays a role in adenoma progression; its frequency is significantly higher in lesions with a more villous morphology.
Proceedings of The National Academy of Sciences, 2002
colorectal tumor predisposition that results from germ-line mutations in the APC gene (chromosome 5q21). FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas. A further group of individuals, so-called ''multiple'' adenoma patients, have a phenotype like AAPC, with 3-99 polyps throughout the colorectum, but mostly have no demonstrable germ-line APC mutation. Routine mutation detection techniques fail to detect a pathogenic APC germ-line mutation in approximately 30% of patients with classical polyposis and 90% of those with AAPC͞multiple adenomas. We have developed a real-time quantitative multiplex PCR assay to detect APC exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC͞multiple adenoma patients with no apparent APC germ-line mutation, deletions were found exclusively in individuals with classical polyposis (7 of 60, 12%). Fine-mapping of the region suggested that the majority (6 of 7) of these deletions encompassed the entire APC locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in APC mutation-negative individuals with classical polyposis seems warranted.
APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis
Gut, 1997
Background-Familial adenomatous polyposis (FAP) is caused by germline mutation of the adenomatous polyposis coli (APC) gene on chromosome Sq. Aims-This study assessed genotypephenotype correlations for extraintestinal lesions in FAP. Methods-Mutations of the APC gene were compared with the occurrence of seven extraintestinal mafestations in 475
Analysis of masked mutations in familial adenomatous polyposis
Proceedings of the National Academy of Sciences, 1999
Familial adenomatous polyposis (FAP) is an autosomal-dominant disease characterized by the development of hundreds of adenomatous polyps of the colorectum. Approximately 80% of FAP patients can be shown to have truncating mutations of the APC gene. To determine the cause of FAP in the other 20% of patients, MAMA (monoallelic mutation analysis) was used to independently examine the status of each of the two APC alleles. Seven of nine patients analyzed were found to have significantly reduced expression from one of their two alleles whereas two patients were found to have full-length expression from both alleles. We conclude that more than 95% of patients with FAP have inactivating mutations in APC and that a combination of MAMA and standard genetic tests will identify APC abnormalities in the vast majority of such patients. That no APC expression from the mutant allele is found in some FAP patients argues strongly against the requirement for dominant negative effects of APC mutations. The results also suggest that there may be at least one additional gene, besides APC, that can give rise to FAP.
Journal of medicine and life
Mutations in adenomatous polyposis coli (APC) gene have not been previously characterized among Romanian patients with colorectal cancer (CRC). We initiate this study to detect the mutations in APC gene in blood and tumor samples collected from 16 patients (10 men and 6 women) and blood samples from 21 first and second degree relatives of the patients. For this the presence of mutations in exons 6, 7, 12, 13, 14 as well as in regions B, L and W of exon 15 was investigated using PCR multiplex. In the same time, we have searched for 5 bp deletions at codon 1061 of APC gene by PAGE and SSCP methods. These methods allowed us to evidence identification of the presence of mutations in samples from 7 individuals. In one patient, was detected a deletion of exon 13th of APC gene both in DNA extracted from blood and tumor samples. Multiple deletions (e.g. in exon 6, 12, and in 15L and 15W regions) in DNA extracted from the tumor sample were detected, but not in DNA probe obtained from blood c...