Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler K W, Vogelstein B, Nakamura Y
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Cancer Res. 1992 Feb 1;52(3):643-5.
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.
APC基因与家族性腺瘤性息肉病相关，被认为是一种与散发性结直肠肿瘤发生相关的肿瘤抑制基因。在此我们报告，在一例结肠癌中，一个长散在重复元件（LINE-1序列）体细胞插入APC基因的最后一个外显子，导致了APC基因的破坏。插入序列由LINE-1共有序列的3'部分和近180个碱基对的聚腺苷酸尾组成。此外，由于观察到一个8碱基对的靶位点重复，怀疑是一个活跃的LINE-1序列的逆转录插入导致了这一插入事件。这是关于移动遗传元件体细胞插入导致肿瘤抑制基因破坏的首次报道。
