To examine the possible involvement of mutations of the APC gene, which is responsible for familial adenomatous polyposis (FAP), in Turcot syndrome, we examined DNAs from TS patients for alterations in this gene by means of ribonuclease protection analysis.
As a reference group for APC mutations in the unselected FAP population, we used the UMD-APC database referenced in the Orphanet portal which includes APC mutation data on 2040 individuals with FAP.
The purpose of this study was to characterize the frequency and nature of somatic adenomatous polyposis coli (APC) gene and K-ras codon 12 mutations in periampullary adenomas and carcinomas in FAP.
These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.
Mutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP using Sanger sequencing.
Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.
To determine whether microsatellite mutations of the adenomatous polyposis coli (APC) gene have pathological or prognostic significance in nephroblastomas and to correlate APC alterations with beta catenin immunoexpression.
The present study, a co-operative project between three European institutes, was aimed at elucidating whether the APC gene in carriers of familial adenomatous polyposis coli (FAP) also causes some genetic sensitivity revealed by DNA damage and the yield of chromosome aberrations in peripheral blood lymphocytes exposed to gamma rays.
In 10-30% of patients with classical familial adenomatous polyposis (FAP) and up to 90% of those with attenuated (<100 colorectal adenomas; AFAP) polyposis, no pathogenic germline mutation in the adenomatous polyposis coli (APC) gene can be identified (APC mutation-negative).
Mutations in the adenomatous polyposis coli (APC) gene cause the hereditary cancer syndrome familial adenomatous polyposis and are implicated in the early stages of sporadic colorectal carcinogenesis.
In this study, we determined the NAT2 genotype in members of one large FAP family and three smaller ones all of which had been shown to harbor the same germline APC gene mutation.
Three different germinal mutations were identified in the mutational clustering region of APC gene by sequencing analysis in five FAP unrelated families.
An analysis was made of the association between development of desmoid and age at colectomy, family history of desmoids, gender, and APC mutation in FAP patients in the Registry (1980-2005) at Mount Sinai Hospital, Toronto, Ontario, Canada.