Impact of cytogenetic and genomic aberrations of the kallikrein locus in ovarian cancer

Bayani, Jane; Paliouras, Miltiadis; Planque, Chris; Shan, Shannon J.C.; Graham, Cassandra; Squire, Jeremy A.; Diamandis, Eleftherios P.

doi:10.1016/j.molonc.2008.07.001

« Previous Next »Molecular Oncology
Volume 2, Issue 3 , Pages 250-260, October 2008

Impact of cytogenetic and genomic aberrations of the kallikrein locus in ovarian cancer

Jane Bayani
- Department of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, M5G 2M9, Canada
Miltiadis Paliouras
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1L5, Canada
Chris Planque
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1L5, Canada
Shannon J.C. Shan
- The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Cassandra Graham
- Department of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, M5G 2M9, Canada
Jeremy A. Squire
- Department of Pathology and Molecular Medicine, Richardson Lab. Queens University, Kingston, Ontario K7L 3N6, Canada
Eleftherios P. Diamandis
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1L5, Canada
- Corresponding author. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5, Ontario, Canada. Tel.: +1 416 586 8443; fax: +1 416 619 5521.

Received 4 June 2008; accepted 14 July 2008. published online 11 August 2008.

Abstract

The tissue kallikrein (KLK) genes are a new source for biomarkers in ovarian cancer. However, there has been no systematic analysis of copy number and structural rearrangements related to their protein expression. Chromosomal rearrangements and copy number changes of the KLK region were studied by FISH with protein levels measured by ELISA. Ovarian cancer and cell lines revealed the KLK region was subject to copy number imbalances or involved in unbalanced translocations and were associated with increased protein expression of KLKs 5, 6, 7, 8, 9, 10 and 11. In this initial study, we introduce the potential for long-range chromosomal effects and copy number as a mechanism for the previously reported aberrant expression of many KLK genes in ovarian cancers.

Keywords: Ovarian cancer, Human kallikreins, Chromosomal rearrangements

Abbreviations: KLK, human tissue kallikrein protein, KLK, human tissue kallikrein gene, ELISA, enzyme-linked immunosorbent assay, PFS, progression-free survival, OS, overall survival, FIGO, Fédération Internationale des Gynaecologistes et Obstetristes, aCGH, array comparative genomic hybridization, mCGH, metaphase comparative genomic hybridization, FISH, fluorescence in situ hybridization, SKY, spectral karyotyping