CRANIAL DESMOID TUMOR-ASSOCIATED WITH HOMOZYGOUS INACTIVATION OF THE ADENOMATOUS POLYPOSIS-COLI GENE IN A 2-YEAR-OLD GIRL WITH FAMILIAL ADENOMATOUS POLYPOSIS

BACKGROUND. Familial adenomatous polyposis (FAP) is a dominantly inher ited disorder characterized by the presence of more than 100 adenomato us polyps in the colon and rectum starting in the second decade of lif e. FAP is associated with extra colonic manifestations, including desm oid tumors. METHODS. A 2-year-old girl presented with a rapidly enlarg ing tumor of the forehead and a family history of FAP. The tumor was c ultured for cytogenetic studies. A DNA linkage study using nanking and intragenic polymorphisms of the adenomatous polyposis coli (APC) gene was performed to identify allele loss in the tumor. Germline mutation identification was by single strand conformation polymorphism analysi s of exon 15 of the APC gene, with subsequent double stranded sequenci ng of fragments with conformational changes. A mutation-induced loss o f a restriction site was used to confirm allele loss in the tumor. RES ULTS. Microscopically, the tumor had desmoid features. Cytogenetic ana lysis of the tumor demonstrated loss of chromosome region 5(q21q22). A truncating adenomatous polyposis coli (APC) gene mutation was identif ied in the leukocyte DNA from the child and her affected father. Linke d DNA markers suggested that the tumor had lost the maternal, wild-typ e allele. A mutation-induced restriction endonuclease site alteration demonstrated hemizygosity of the mutant sequence in the tumor DNA. CON CLUSIONS. These findings are compatible with the presence of a ''secon d hit'' inactivation of the APC gene and implicate this gene in the pa thogenesis of desmoid tumors. (C) 1996 American Cancer Society.