Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome

David A. Engler, Sumeet Gupta, Whitfield B. Growdon, Ronny I. Drapkin, Mai Nitta, Petra A. Sergent, Serena F. Allred, Jenny Gross, Michael T. Deavers, Wen Lin Kuo, Beth Y. Karlan, Bo R. Rueda, Sandra Orsulic, David M. Gershenson, Michael J. Birrer, Joe Gray, Gayatry Mohapatra

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups.

Original languageEnglish (US)
Article numbere30996
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 15 2012
Externally publishedYes

Fingerprint

Genetic Markers
carcinoma
Tumors
Genes
Genome
Carcinoma
Cluster Analysis
neoplasms
genetic markers
tumor suppressor genes
ovarian neoplasms
genome
oncogenes
DNA
Tumor Suppressor Genes
Oncogenes
Ovarian Neoplasms
Survival
Neoplasms
oligonucleotides

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Engler, D. A., Gupta, S., Growdon, W. B., Drapkin, R. I., Nitta, M., Sergent, P. A., ... Mohapatra, G. (2012). Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. PLoS One, 7(2), [e30996]. https://doi.org/10.1371/journal.pone.0030996

Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. / Engler, David A.; Gupta, Sumeet; Growdon, Whitfield B.; Drapkin, Ronny I.; Nitta, Mai; Sergent, Petra A.; Allred, Serena F.; Gross, Jenny; Deavers, Michael T.; Kuo, Wen Lin; Karlan, Beth Y.; Rueda, Bo R.; Orsulic, Sandra; Gershenson, David M.; Birrer, Michael J.; Gray, Joe; Mohapatra, Gayatry.

In: PLoS One, Vol. 7, No. 2, e30996, 15.02.2012.

Research output: Contribution to journalArticle

Engler, DA, Gupta, S, Growdon, WB, Drapkin, RI, Nitta, M, Sergent, PA, Allred, SF, Gross, J, Deavers, MT, Kuo, WL, Karlan, BY, Rueda, BR, Orsulic, S, Gershenson, DM, Birrer, MJ, Gray, J & Mohapatra, G 2012, 'Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome', PLoS One, vol. 7, no. 2, e30996. https://doi.org/10.1371/journal.pone.0030996
Engler, David A. ; Gupta, Sumeet ; Growdon, Whitfield B. ; Drapkin, Ronny I. ; Nitta, Mai ; Sergent, Petra A. ; Allred, Serena F. ; Gross, Jenny ; Deavers, Michael T. ; Kuo, Wen Lin ; Karlan, Beth Y. ; Rueda, Bo R. ; Orsulic, Sandra ; Gershenson, David M. ; Birrer, Michael J. ; Gray, Joe ; Mohapatra, Gayatry. / Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. In: PLoS One. 2012 ; Vol. 7, No. 2.
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