Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma.

Purpose: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member.

Methods: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus.

Results: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative.

Conclusions: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.