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Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas

T Z Parris1, A Kovács2, S Hajizadeh2

  • 1Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Oncogenesis
|March 26, 2014
PubMed

Insights

Genomic alterations in the 8p11-p12 region and MYC oncogene coamplification are common in breast cancer. Aberrant DNA methylation also contributes to aggressive tumor phenotypes in these patients.

Area of Science:

  • Genomics
  • Cancer Biology
  • Epigenetics

Background:

  • Genetic and epigenetic crosstalk influences oncogene and tumor suppressor gene activity.
  • The 8p11-p12 chromosomal region is frequently altered in cancers, particularly breast carcinoma, where amplification correlates with poor prognosis.

Purpose of the Study:

  • To investigate the genomic and epigenomic landscape of the 8p11-p12 region in breast carcinoma.
  • To identify potential drivers of aggressive tumor phenotypes associated with 8p11-p12 amplification.

Main Methods:

  • Integrative genomics screen including DNA copy number, transcriptional, and DNA methylation profiling.
  • Analysis of 229 primary invasive breast carcinoma samples.

Main Results:

  • Identified substantial coamplification of the 8p11-p12 region and the MYC oncogene (8q24.21).
  • Detected aberrant methylation and transcriptional patterns for multiple genes within the 8q12.1-q24.22 genomic region.
  • Observed a correlation between 8p11-p12 amplification, MYC activity, and aberrant DNA methylation in aggressive breast tumors.

Conclusions:

  • MYC oncogene activity and aberrant DNA methylation play crucial roles in the aggressive phenotype of breast carcinomas with 8p11-p12 amplification.
  • These findings highlight potential therapeutic targets for managing aggressive breast cancer subtypes.

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