COEXISTENCE OF SOMATIC AND GERM-LINE MUTATIONS OF APC GENE IN DESMOIDTUMORS FROM PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS

Desmoid tumors, which are locally invasive with recurrence but without metastasis, are frequently observed in patients with familial adenoma tous polyposis after abdominal surgery or during pregnancy. This study analyzed mutation of the adenomatous polyposis coli gene in 8 desmoid tumors from 7 familal adenomatous polyposis patients using polymerase chain reaction-single-strand conformation polymorphism and the direct sequencing method. Seven somatic mutations, 1 somatic allele loss, an d 6 germ-line mutations were detected. The majority of adenomatous pol yposis coli gene mutations were deletions of 1 to 19 base pairs in exo n 15, and all mutations led to the formation of stop codons. A somatic mutation with repetition of 82 base pairs from codon 1399 to 1426 was also observed in a desmoid, which was most likely caused by an error during replication or repair replication. No mutation was detected in exons 1 to 2 of H-ras, K-ras, and N-ras genes and in exons 5 to 8 of p 53 gene, in these tumors. The simultaneous existence of somatic and ge rm-line alterations of adenomatous polyposis coli gene observed in all 8 tumors strongly suggests that inactivation of both alleles of adeno matous polyposis coli gene is involved in the development of desmoid t umors.