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High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival

Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of...

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Autores principales: Baumbusch, Lars O., Helland, Åslaug, Wang, Yun, Liestøl, Knut, Schaner, Marci E., Holm, Ruth, Etemadmoghadam, Dariush, Alsop, Kathryn, Brown, Pat, Mitchell, Gillian, Fereday, Sian, DeFazio, Anna, Bowtell, David D. L., Kristensen, Gunnar B., Lingjærde, Ole Christian, Børresen-Dale, Anne-Lise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553118/
https://www.ncbi.nlm.nih.gov/pubmed/23372714
http://dx.doi.org/10.1371/journal.pone.0054356
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author Baumbusch, Lars O.
Helland, Åslaug
Wang, Yun
Liestøl, Knut
Schaner, Marci E.
Holm, Ruth
Etemadmoghadam, Dariush
Alsop, Kathryn
Brown, Pat
Mitchell, Gillian
Fereday, Sian
DeFazio, Anna
Bowtell, David D. L.
Kristensen, Gunnar B.
Lingjærde, Ole Christian
Børresen-Dale, Anne-Lise
author_facet Baumbusch, Lars O.
Helland, Åslaug
Wang, Yun
Liestøl, Knut
Schaner, Marci E.
Holm, Ruth
Etemadmoghadam, Dariush
Alsop, Kathryn
Brown, Pat
Mitchell, Gillian
Fereday, Sian
DeFazio, Anna
Bowtell, David D. L.
Kristensen, Gunnar B.
Lingjærde, Ole Christian
Børresen-Dale, Anne-Lise
author_sort Baumbusch, Lars O.
collection PubMed
description Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents.
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spelling pubmed-35531182013-01-31 High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival Baumbusch, Lars O. Helland, Åslaug Wang, Yun Liestøl, Knut Schaner, Marci E. Holm, Ruth Etemadmoghadam, Dariush Alsop, Kathryn Brown, Pat Mitchell, Gillian Fereday, Sian DeFazio, Anna Bowtell, David D. L. Kristensen, Gunnar B. Lingjærde, Ole Christian Børresen-Dale, Anne-Lise PLoS One Research Article Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents. Public Library of Science 2013-01-23 /pmc/articles/PMC3553118/ /pubmed/23372714 http://dx.doi.org/10.1371/journal.pone.0054356 Text en © 2013 Baumbusch et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Baumbusch, Lars O.
Helland, Åslaug
Wang, Yun
Liestøl, Knut
Schaner, Marci E.
Holm, Ruth
Etemadmoghadam, Dariush
Alsop, Kathryn
Brown, Pat
Mitchell, Gillian
Fereday, Sian
DeFazio, Anna
Bowtell, David D. L.
Kristensen, Gunnar B.
Lingjærde, Ole Christian
Børresen-Dale, Anne-Lise
High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
title High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
title_full High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
title_fullStr High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
title_full_unstemmed High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
title_short High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
title_sort high levels of genomic aberrations in serous ovarian cancers are associated with better survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553118/
https://www.ncbi.nlm.nih.gov/pubmed/23372714
http://dx.doi.org/10.1371/journal.pone.0054356
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