Detecting Gene Copy Number Fluctuations in Tumor Cells by Microarray Analysis of Genomic Representations

  1. Robert Lucito1,5,
  2. Joseph West1,
  3. Andrew Reiner1,
  4. Joan Alexander1,
  5. Diane Esposito1,
  6. Bhubaneswar Mishra2,
  7. Scott Powers3,
  8. Larry Norton4, and
  9. Michael Wigler1
  1. 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA; 2Courant Institute, New York University, New York, New York 10012, USA; 3Tularik, Greenlawn, New York 11740, USA; 4Memorial Sloan-Kettering, Division of Solid Tumor Oncology, New York, New York 10021, USA

Abstract

In this work, we explore the use of representations in conjunction with DNA microarray technology to measure gene copy number changes in cancer. We demonstrate that arrays of DNA probes derived from low-complexity representations can be used to detect amplifications, deletions, and polymorphic differences when hybridized to representations of genomic DNA. The method is both reproducible and verifiable, and is applicable even to microscopic amounts of primary tumors. We also present a mathematical model for array performance that is useful for designing and understanding DNA microarray hybridization protocols. The future applications and challenges of this approach are discussed.

Footnotes

  • 5 Corresponding author.

  • E-MAIL lucito{at}cshl.org; FAX (516) 367-8381.

  • Article and publication are at www.genome.org/cgi/doi/10.1101/gr138300

    • Received February 24, 2000.
    • Accepted September 9, 2000.
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