Sporadic breast cancer patients' germline DNA exhibit an AT-rich microsatellite signature

Cristi L. Galindo, Lauren J. McIver, Hongseok Tae, John F. McCormick, Michael A. Skinner, Ina Hoeschele, Cheryl M. Lewis, John D. Minna, David A. Boothman, Harold R. Garner

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11 Scopus citations

Abstract

Using a custom CGH-like oligonucleotide array to measure the global microsatellite content in the genomes of 72 cancer, cancer-free, and high risk patient and cell line samples (56 germline DNA and 16 in tumor or tumor cell line DNA) we found a unique, reproducible, and statistically significant pattern of 18 motif-specific microsatellite families (out of 962 possible 1-6 mer repeats) in breast cancer patient germline and tumor DNA, but not in germline DNA of cancer-free volunteer controls or in breast cancer patients with BRCA1/2 mutations. These high-similarity A/T rich repetitive motifs were also more pronounced in the germlines and tumors of colon cancer tumor patients (3/6 samples) and microsatellite unstable colon cancer cell lines; however, germline DNA of sporadic breast cancer patients exhibited the largest global content shift for those motifs with extreme AT/GC ratios. These results indicate that global microsatellite variability is complex, suggest the existence of a previously unknown genomic destabilization mechanism in breast cancer patients' germline DNA, and warrant further testing of such microsatellite variability as a predictor of future breast cancer development.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalGenes Chromosomes and Cancer
Volume50
Issue number4
DOIs
StatePublished - Apr 1 2011

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ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Galindo, C. L., McIver, L. J., Tae, H., McCormick, J. F., Skinner, M. A., Hoeschele, I., Lewis, C. M., Minna, J. D., Boothman, D. A., & Garner, H. R. (2011). Sporadic breast cancer patients' germline DNA exhibit an AT-rich microsatellite signature. Genes Chromosomes and Cancer, 50(4), 275-283. https://doi.org/10.1002/gcc.20853