Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome.
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 i...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3280266?pdf=render |
| _version_ | 1819265338996424704 |
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| author | 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 W Gray Gayatry Mohapatra |
| author_facet | 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 W Gray Gayatry Mohapatra |
| author_sort | David A Engler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T20:43:48Z |
| format | Article |
| id | doaj.art-a83f73dacb5149db95173f62545a1e15 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:43:48Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a83f73dacb5149db95173f62545a1e152022-12-21T17:31:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3099610.1371/journal.pone.0030996Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome.David A EnglerSumeet GuptaWhitfield B GrowdonRonny I DrapkinMai NittaPetra A SergentSerena F AllredJenny GrossMichael T DeaversWen-Lin KuoBeth Y KarlanBo R RuedaSandra OrsulicDavid M GershensonMichael J BirrerJoe W GrayGayatry MohapatraOvarian 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.http://europepmc.org/articles/PMC3280266?pdf=render |
| spellingShingle | 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 W Gray Gayatry Mohapatra Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. PLoS ONE |
| title | Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. |
| title_full | Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. |
| title_fullStr | Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. |
| title_full_unstemmed | Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. |
| title_short | Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. |
| title_sort | genome wide dna copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome |
| url | http://europepmc.org/articles/PMC3280266?pdf=render |
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