Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer

Cancer Res. 1992 Feb 1;52(3):643-5.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Base Sequence
  • Blotting, Southern
  • Colonic Neoplasms / genetics*
  • DNA / genetics
  • DNA / isolation & purification
  • DNA Transposable Elements*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • Exons
  • Genes, Tumor Suppressor*
  • Humans
  • Intestinal Mucosa / physiopathology
  • Molecular Sequence Data
  • Mutagenesis, Insertional*
  • Repetitive Sequences, Nucleic Acid
  • Retroviridae / genetics
  • Sequence Homology, Nucleic Acid

Substances

  • DNA Transposable Elements
  • DNA, Neoplasm
  • DNA

Associated data

  • GENBANK/S44781
  • GENBANK/S44786
  • GENBANK/S44787
  • GENBANK/S72766
  • GENBANK/S72767
  • GENBANK/S72768
  • GENBANK/S72769
  • GENBANK/S72771
  • GENBANK/S78214
  • GENBANK/X63098