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Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis

Gromoslaw A Smolen1, Beth Muir, Gayatry Mohapatra

  • 1Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.

Cancer Research
|April 6, 2006
PubMed

Insights

Loss of Brca1 and Trp53 genes in mice initiated high-level Met gene amplification in mammary tumors. This amplification, found on double minute chromosomes, suggests potential secondary genetic hits in human BRCA1-initiated breast cancer.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Brca1 and Trp53 gene loss are critical in initiating mammary tumors.
  • Gene copy number alterations play a role in tumor progression.
  • Met receptor tyrosine kinase is implicated in various cancers.

Purpose of the Study:

  • To identify gene copy number alterations in mouse mammary tumors initiated by Brca1 and Trp53 loss.
  • To investigate the role of Met gene amplification in these tumors.
  • To explore potential parallels with human breast cancer.

Main Methods:

  • Gene copy number screening in mouse mammary tumor models.
  • Analysis of genetic alterations, specifically Met amplification.
  • Characterization of chromosomal localization of amplifications.

Main Results:

  • High-level amplification of the wild-type Met gene was observed in 73% of mouse mammary tumors with Brca1 and Trp53 loss.
  • Met amplification was associated with unstable double minute chromosomes.
  • This specific amplification was unique to mouse tumors driven by Brca1 and Trp53 loss.

Conclusions:

  • The Met gene amplification is a dominant secondary genetic lesion in the Brca1/Trp53 mouse model of breast cancer.
  • While analogous MET amplification is not found in human breast cancers, this mouse model provides insights.
  • Recurrent secondary genetic hits may also occur in human BRCA1-initiated breast cancer.

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