Four regions of allelic imbalance on 17q12-qter associated with high-grade breast tumors

Authors

  • Sarah J. Plummer,

    1. Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    Search for more papers by this author
  • Mark J. Paris,

    1. Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    Search for more papers by this author
  • Jonathan Myles,

    1. Departments of Anatomic and Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio
    Search for more papers by this author
  • Raymond Tubbs,

    1. Departments of Anatomic and Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio
    Search for more papers by this author
  • Joseph Crowe,

    1. The Cancer Center, The Cleveland Clinic Foundation, Cleveland, Ohio
    2. Department of General Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio
    3. The Breast Center, The Cleveland Clinic Foundation, Cleveland, Ohio
    Search for more papers by this author
  • Graham Casey

    Corresponding author
    1. Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    2. The Cancer Center, The Cleveland Clinic Foundation, Cleveland, Ohio
    • Department of Cancer Biology, NN10, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
    Search for more papers by this author

Abstract

Rearrangements or loss of chromosome 17 are frequent events in breast tumors. Chromosome 17 contains at least four genes implicated in breast cancer (TP53, ERBB2 (Her2/neu), BRCA1, and NM23), as well as other putative tumor suppressor genes and oncogenes implicated in loss of heterozygosity or allelic imbalance studies. Allelic imbalance represents the addition or loss of genetic material in tumor samples, providing circumstantial evidence for the location of cancer related genes. We have analyzed a panel of 85 breast tumor/normal tissue pairs with 21 PCR-based short tandem repeat (STR) markers located at 17q12-qter to more precisely define regions of allelic imbalance and to determine their relation to clinical parameters. Our analysis revealed at least four common regions of allelic imbalance: proximal to BRCA1, including D17S800 (17q12); distal to NM23 around D17S787 (17q22); near the growth hormone (GH) locus, at D17S948 (17q23-24); and between markers D17S937 and D17S802 (17q25). These data also reveal that loss (or gain) of 17q genetic material correlates with poorly differentiated (grade III) tumors (P = <0.001), high S phase fraction (P = 0.034), and positive TP53 immunohistochemical staining (P = 0.011). However, steroid receptor status, ERBB2 (Her2/neu) staining, and aneuploidy do not correlate with allelic imbalance at 17q. Genes Chromosomes Cancer 20:354–362, 1997. © 1997 Wiley-Liss, Inc.

Ancillary