Genetic Analysis of Early/Late Stage Ovarian Tumors

Genetic Analysis of Early- versus Late-Stage Ovarian Tumors

1 Viji Shridhar, John Lee, Ajay Pandita, Steve Iturria, Rajeswari Avula, Julie Staub, Mike Morrissey, Eric Calhoun, Ami Sen, Kimberly Kalli, Gary Keeney, Patrick Roche, William Cliby, Karen Lu, Rosemarie Schmandt, Gordon B. Mills, Robert C. Bast, Jr., C. David James, Fergus J. Couch, Lynn C. Hartmann, Jim Lillie and David I. Smith2

Departments of Experimental Pathology, Division of Laboratory Medicine Health Sciences Research, Division of Biostatistics, Molecular Pharmacology and Endocrine Research, Gynecologic Surgery, Division of Anatomic Pathology, and Oncology, Section of Gynecologic Surgery, The Mayo Clinic, Rochester, Minnesota 55905; Millennium Predictive Medicine, Cambridge, Massachusetts; and Departments of Gynaecologic Oncology, Molecular Therapeutics, and Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030

In the United States, ovarian cancer is the fourth most common cause of cancer-related deaths among women. The most important prognostic factor for this cancer is tumor stage, or extent of disease at diagnosis. Although women with low-stage tumors have a relatively good prognosis, most women diagnosed with late-stage disease eventually succumb to their cancer.

In an attempt to understand early events in ovarian carcinogenesis, and to explore steps in its progression, we have applied multiple molecular genetic techniques to the analysis of 21 early-stage (stage I/II) and 17 advanced-stage (stage III/IV) ovarian tumors. These techniques included expression profiling with cDNA microarrays containing approximately 18,000 expressed sequences, and comparative genomic hybridization to address the chromosomal locations of copy number gains as well as losses.

Results from the analysis indicate that early-stage ovarian cancers exhibit profound alterations in gene expression, many of which are similar to those identified in late-stage tumors.

However, differences observed at the genomic level suggest differences between the early- and late-stage tumors and provide support for a progression model for ovarian cancer development.

Cancer Research 61, 5895-5904, August 1, 2001] 2001 American Association for Cancer Research

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