DNA sequences amplified in cancer cells: an interface between tumor biology and human genome analysis

Yosef Shiloh, Orna Mor, Ari Manor, Irit Bar-Am, Galit Rotman, James Eubanks, Mordechai Gutman, Guglielmina N. Ranzani, Jane Houldsworth, Glen Evans, Lydia Avivi

Research output: Contribution to journalArticlepeer-review

Abstract

There is growing evidence that amplification of specific genes is associated with tumor progression. While several proto-oncogenes are known to be activated by amplification, it is clear that not all the genes involved in DNA amplification in human tumors have been discovered. Our approach to the identification of such genes is based on the 'reverse genetics' methodology. Anonymous amplified DNA fragments are cloned by virtue of their amplification in a given tumor. These sequences are mapped in the normal genome and hence define a new genetic locus. The amplified domain is isolated by long-range cloning and analyzed along three lines of investigation: new genes are sought that can explain the biological significance of the amplification; the structure of the domain is studied in normal cells and in the amplification unit in the cancer cell; attempts are made to identify molecular probes of diagnostic value within the amplified domain. This application of genome technology to cancer biology is demon-strated in our study of a new genomic domain at chromosome 10q26 which is amplified specifically in human gastric carcinomas.

Original languageEnglish
Pages (from-to)329-337
Number of pages9
JournalMutation Research - Reviews in Genetic Toxicology
Volume276
Issue number3
DOIs
StatePublished - May 1992

Keywords

  • Cancer
  • DNA amplification
  • Human genome
  • Molecular oncology
  • Oncogenes

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