HEREDITARY DESMOID DISEASE DUE TO A FRAMESHIFT MUTATION AT CODON-1924OF THE APC GENE

Desmoid tumors are slowly growing fibrous tumors highly resistant to t herapy and often fatal. Here, we report hereditary desmoid disease (HD D), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early develop ment of premalignant adenomatous polyps in the colorectum due to chain -terminating mutations of the APC gene. In general, one or more member s in similar to 10% of the FAP families manifest desmoid tumors. Affec ted individuals from the HDD kindred are characterized by multifocal f ibromatosis of the paraspinal muscles, breast, occiput, arms, lower ri bs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and othe r congenital features were also observed. We show that HDD segregates with an unusual germline chain-terminating mutation at the 3' end of t he APC gene (codon 1924) with somatic loss of the wild-type allele lea ding to tumor development.