Abstract
BackgroundFamilial adenomatous polyposis, an autosomal dominant inherited disease caused by germline mutations within the APC gene, is characterized by early onset colorectal cancer as a consequence of the intrinsic phenotypic feature of multiple colorectal adenomatic polyps. The genetic investigation of Greek adenomatous polyposis families was performed in respects to APC and MUTYH germline mutations. Additionally, all available published mutations were considered in order to define the APC mutation spectrum in Greece.MethodsA cohort of 25 unrelated adenomatous polyposis families of Greek origin has been selected. Genetic testing included direct sequencing of APC and MUTYH genes. APC gene was also checked for large genomic rearrangements by MLPA.ResultsAnalysis of the APC gene performed in a Greek cohort of twenty five FAP families revealed eighteen different germline mutations in twenty families (80%), four of which novel. Mutations were scattered between exon 3 and codon 1503 of exon 15, while no large genomic rearrangements were identified.ConclusionThis concise report describes the spectrum of all APC mutations identified in Greek FAP families, including four novel mutations. It is concluded that the Greek population is characterized by genetic heterogeneity, low incidence of genomic rearrangements in APC gene and lack of founder mutation in FAP syndrome.
Highlights
Familial adenomatous polyposis, an autosomal dominant inherited disease caused by germline mutations within the adenomatous polyposis coli (APC) gene, is characterized by early onset colorectal cancer as a consequence of the intrinsic phenotypic feature of multiple colorectal adenomatic polyps
The aim of this study is to describe the complete APC mutation spectrum identified in Greek familial adenomatous polyposis (FAP) families and to correlate it to the phenotype
The distribution of germline mutations identified, occurring over the 5’ half of the APC gene, is in concert with most reports, while quite interesting is the low frequency of the two hotspot mutations identified in most populations studied
Summary
An autosomal dominant inherited disease caused by germline mutations within the APC gene, is characterized by early onset colorectal cancer as a consequence of the intrinsic phenotypic feature of multiple colorectal adenomatic polyps. An attenuated form of disease, characterized by the later onset and smaller number of polyps, is caused by mutations on the extreme 5’ end or the 3’ end [13] or the alternatively spliced region of exon 9 of the gene [14,15,16] In the latter case, the mutated codon can be ruled out during the normal splicing occurring in colonic mucosa, resulting in a milder phenotype. Both isoforms are present in normal tissues, the expression of which is tissue-specific, with the full version being more abundant in most tissues [1]
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