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Department of Biochemistry, Cancer Institute, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan [Y. Mik., I. N., A. H., Y. Miy., Y. N.]; Second Department of Surgery, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663, Japan [Y. Mik., J. U.]; and Molecular Genetics Laboratory, The Johns Hopkins Oncology Center, Baltimore, Maryland 21231 [K. K., B. V.]
The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.
1 This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture and Science, Japan, and Grants for the Vehicle Racing Commemorative Foundation, the Clayton Fund, and National Cancer Institute.
2 To whom requests for reprints should be addressed.
Received 9/ 4/91. Accepted 11/13/91.
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