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Coexistence of Somatic and Germ-Line Mutations of APC Gene in Desmoid Tumors from Patients with Familial Adenomatous Polyposis¹

Department of Biochemistry, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113 [M. Mi., M. K., R. K-Y., M. E., K. T., H. T., M. Mu.], Department of Surgery, Tokyo Medical and Dental University [M. E., T. I.], and Department of Surgery, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, 113, Japan [T. M.]; and Department of Surgery, Jichi Medical School, Tochigi, 329-04, Japan [F. K.]

Desmoid tumors, which are locally invasive with recurrence but without metastasis, are frequently observed in patients with familial adenomatous 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, and 6 germ-line mutations were detected. The majority of adenomatous polyposis coli gene mutations were deletions of 1 to 19 base pairs in exon 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 p53 gene, in these tumors. The simultaneous existence of somatic and germ-line alterations of adenomatous polyposis coli gene observed in all 8 tumors strongly suggests that inactivation of both alleles of adenomatous polyposis coli gene is involved in the development of desmoid tumors.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education and Culture of Japan, and by the Naito Foundation.

² To whom requests for reprints should be addressed.

Received 7/19/93. Accepted 9/16/93.

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