Cloning of a breast cancer homozygous deletion junction narrows the region of search for a 3p21.3 tumor suppressor gene

Yoshitaka Sekido, Mohsen Ahmadian, Ignacio I. Wistuba, Farida Latif, Scott Bader, Ming Hui Wei, Fuh Mei Duh, Adi F. Gazdar, Michael I. Lerman, John D. Minna

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Chromosome 3p abnormalities and allele loss are frequent in lung and breast cancers, and several lung cancer cell lines exhibit homozygous deletions of 3p indicating potential sites of tumor suppressor genes at regions 3p21.3, 3p14.2 and 3p12. We have identified and characterized a new 3p21.3 homozygous deletion in a breast cancer cell line and the primary tumor that overlaps those previously described in small cell lung cancer (SCLC). This homozygous deletion is approximately 220 kb in length and represents a somatically acquired change in the primary breast canter. Cloning and sequencing of the breakpoint demonstrated that this resulted from an interstitial deletion and precisely pinpoints this deletion within the three SCLC homozygous deletions previously reported. This deletion significantly narrows the minimum common deleted region to 120 kb and is distinct from the previously reported region that suppresses tumor formation of the murine A9 fibrosarcoma cells. These findings suggest that a common homozygous deletion region on 3p21.3 is important in both lung and breast cancers. It is likely that this very well characterized region either contains one tumor suppressor gene common to both tumor types or two closely linked tumor suppressor genes specific for each tumor.

Original languageEnglish (US)
Pages (from-to)3151-3157
Number of pages7
JournalOncogene
Volume16
Issue number24
DOIs
StatePublished - Jun 18 1998

Keywords

  • Breakpoint cloning
  • Breast cancer
  • Chromosome 3
  • Homozygous deletion
  • Lung cancer
  • Somatic mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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