Research Article

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

  1. Cristi L. Galindo1,
  2. Lauren J. McIver1,
  3. Hongseok Tae1,
  4. John F. McCormick1,
  5. Michael A. Skinner2,3,
  6. Ina Hoeschele4,
  7. Cheryl M. Lewis2,
  8. John D. Minna5,6,7,8,
  9. David A. Boothman8,
  10. Harold R. Garner1,*

Article first published online: 14 JAN 2011

DOI: 10.1002/gcc.20853

Issue

Genes, Chromosomes and Cancer

Genes, Chromosomes and Cancer

Volume 50, Issue 4, pages 275–283, April 2011

Additional Information

How to Cite

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. and Garner, H. R. (2011), Sporadic breast cancer patients' germline DNA exhibit an AT-rich microsatellite signature. Genes Chromosom. Cancer, 50: 275–283. doi: 10.1002/gcc.20853

Author Information

  1. 1

    Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA

  2. 2

    Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX

  3. 3

    Children's Medical Center, Dallas, TX

  4. 4

    Department of Statistics, Virginia Polytechnic Institute and State University, Blacksburg, VA

  5. 5

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX

  6. 6

    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

  7. 7

    Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX

  8. 8

    Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX

*Virginia Bioinformatics Institute, Virginia Polytechnic and State University, Washington Street (0477) Blacksburg VA 24061-0477, USA

  1. †

    Supported by: NIH, 5-T32-HL07360-28; NIH/NCI SPORE in Lung Cancer, P50CA70907; Virginia Bioinformatics Institute Director's Funds, the P.O'B. Montgomery Distinguished Chair; Hudson Foundation.

Publication History

  1. Issue published online: 11 FEB 2011
  2. Article first published online: 14 JAN 2011
  3. Manuscript Accepted: 13 DEC 2010
  4. Manuscript Received: 8 NOV 2010

Funded by

  • NIH. Grant Number: 5-T32-HL07360-28
  • NIH/NCI SPORE in Lung Cancer. Grant Number: P50CA70907
  • Virginia Bioinformatics Institute Director's Funds
  • P.O'B. Montgomery Distinguished Chair
  • Hudson Foundation

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (519K)

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. © 2011 Wiley-Liss, Inc.

View Full Article with Supporting Information (HTML) Get PDF (519K)