APC Promoter Deletion in Classic Familial Adenomatous Polyposis

The ~80% of individuals with classic familial adenomatous polyposis (FAP) have detectable mutations in the coding sequence of the adenomatous polyposis coli (APC) gene. To investigate the 20% of families without detectable causative mutations, we used exome sequencing and second-generation sequencing of the APC locus including non-coding regions. We identified a novel ~11kb deletion 44kb upstream of APC that was present only in affected individuals of three kindreds. SNP analysis showed that this ~11kb deletion was accompanied by silencing of one of the APC alleles in blood-derived RNA of affected individuals. ]]>
Inclusion Criteria: Individuals with classic familial adenomatous polyposis were tested for known APC mutations with Colaris AP® (Myriad Genetic Laboratories). Those without detectable mutations by Colaris AP® and consenting family members were enrolled. Exclusion Criteria: Individuals with sporadic gastrointestinal cancer or a family history of cancer not suggestive of hereditary or familial diseases were excluded.]]>