Journal
CLINICAL GENETICS
Volume 88, Issue 4, Pages 360-365Publisher
WILEY
DOI: 10.1111/cge.12503
Keywords
allelic imbalance; APC; APC promoter 1B; colon cancer; familial adenomatous polyposis; founder mutation
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Funding
- NCI [P01-CA073992, R01-CA040641]
- Cancer Center Support Grant [P30-CA42014]
- Utah Cancer Registry
- Lloyd David and Carlye Cannon Wattis Foundation
- Huntsman Cancer Foundation
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Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation-dependent probe amplification (MLPA) probes specific for APC promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the APC locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele-specific expression of APC mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42-98%, depending on tissue type. This study confirms the importance of APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States.
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