APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP).
Expression of APC is decreased in mutation negative cases and this appears to be a promising indicator of FAP predisposition, while for MUTYH gene, mutation is associated to reduced mRNA expression.
Given that FAP fibroblasts showed heightened sensitivity to transformation by KiMSV and SV40 including elevated levels of the p53 protein, events controlled in large measure by the Ras suppressor protein-1 (RSU-1) and oncogenic DJ-1, here we show decreased RSU1 and augmented DJ-1 expression in both fibroblasts and crypt-derived epithelial cells from morphologically normal colonic mucosa of FAP gene-carriers.
Familial adenomatous polyposis [FAP (OMIM 175100)] is an autosomal dominant colorectal cancer predisposition syndrome characterized by hundreds to thousands of colonic polyps and, if untreated by a combination of screening and/or surgical intervention, an approximately 99% lifetime risk of colorectal cancer.
Patients in whom no mutation is identified through this mutation protocol, may be sub-cohorts representing a different FAP pathogenesis including MYH associated polyposis and somatic cell mosaicism for APC gene mutations.
These are important, both in inherited syndromes (familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer [HNPCC], respectively) and in sporadic cancers.Other less well defined pathways exist.
Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted.
The first comparative study on predicting post-test distress (conceptualised by intrusion and avoidance, measured with the Impact of Event Scale) after presymptomatic genetic testing for Huntington's disease (HD, n=25), cancer syndromes (familial adenomatous polyposis (FAP, n=23)), and hereditary breast and ovarian cancer (HBOC, n=10) is reported.
In a comparative study on the effects of predictive DNA testing for late onset disorders, pre-test psychological distress was assessed in people at risk for Huntington's disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45).
Correlation between the molecular analysis and ophthalmic examinations, performed without knowledge of clinical and genetic status respectively, provided additional evidence in favour of the view that the range of phenotypic expression in FAP may result from different allelic manifestations of APC mutations.
One hundred and eighteen subjects with familial adenomatous polyposis (FAP) and 80 of their relatives who were at low risk (< 0.01) of carrying the FAP gene were scored by one of us (BJ) or by colleagues to assess the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE).
The recent identification of the familial adenomatous polyposis (FAP) gene (designated as APC) enables conclusive genetic testing of at-risk family members for the specific mutation in families in which the germline gene mutation has been characterized.
Retinoblastoma (RB) and the familial adenomatous polyposis/colorectal cancer (FAP/CRC) complex provide well-characterised examples of multistage carcinogenesis and inheritance of a predisposition to cancer.
The original probe that established linkage to the FAP locus (C11p11) has limited utility for family studies because of low heterozygosity and distance from the FAP gene.