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Construction of a chromosome 17 transcriptome in serous ovarian cancer identifies differentially expressed genes
  1. P. M. Wojnarowicz*,
  2. A. Breznan*,
  3. S. L. Arcand,
  4. A. Filali-Mouhim,
  5. D. M. Provencher,§,
  6. A.-M. Mes-Masson, and
  7. P. N. Tonin*,,
  1. * Department of Human Genetics, McGill University, Montreal, Canada;
  2. The Research Institute of the McGill University Health Centre, Montreal, Canada;
  3. Centre de recherche du Centre Hospitalier de l'Université de Montréal/Institut du Cancer de Montréal, Montréal, Canada;
  4. § Division de gynécologie oncologique, Université de Montréal, Montréal, Canada;
  5. Département de médicine, Université de Montréal, Montréal, Canada; and
  6. Department of Medicine, McGill University, Montreal, Canada
  1. Address correspondence and reprint requests to: Patricia N. Tonin, PhD, Associate Professor, McGill University, Medical Genetics, Room L10-120, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4. Email: patricia.tonin{at}mcgill.ca

Abstract

Cytogenetic, molecular genetic, and functional analyses have implicated chromosome 17 genes in epithelial ovarian cancer (EOC). To further characterize the contribution of chromosome 17 genes in EOC, the Affymetrix U133A GeneChip was used to perform transcriptome analyses of 15 primary cultures of normal ovarian surface epithelial (NOSE) cells and 17 malignant ovarian tumor (TOV) samples of the serous histopathologic subtype. A two-way comparative analysis of 776 known genes and expressed sequences identified 253 genes that exhibited at least a threefold difference in expression in at least one TOV sample compared to the mean of NOSE samples. Within this data set, 99 of the 253 (39.1%) genes exhibited similar patterns of expression across all tested samples, suggesting a high degree of concordance in the chromosome 17 transcriptome. This observation was supported by hierarchical clustering analysis that segregated the TOV and NOSE samples into two separate groups. There were 77 genes that were differentially expressed in at least 50% of the TOV samples. Five genes (AdoRA2B at 17p12, CCL2 at 17q12, ACLY at 17q21.2, WIPI1 at 17q24.2, and SLC16A3 at 17q25.3) were significantly (P< 5.13E−11) differentially expressed at least threefold in all serous TOV samples, and all five genes were underexpressed in these TOV samples as compared to the NOSE samples. Interestingly, several of these differentially expressed genes have been previously associated with response to hypoxia.

  • chromosome 17
  • expression microarray
  • hypoxia
  • ovarian cancer
  • transcriptome

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