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

Lars O. Baumbusch, Åslaug Helland, Yun Wang, Knut Liestøl, Marci E. Schaner, Ruth Holm, Dariush Etemadmoghadam, Kathryn Alsop, Pat Brown, Gillian Mitchell, Sian Fereday, Anna DeFazio, David D.L. Bowtell, Gunnar B. Kristensen, Ole Christian Lingjærde, Anne Lise Børresen-Dale

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere54356
JournalPLoS ONE
Volume8
Issue number1
DOIs
StatePublished - 29 Jan 2013
Externally publishedYes

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