TY - JOUR
T1 - High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
AU - Baumbusch, Lars O.
AU - Helland, Åslaug
AU - Wang, Yun
AU - Liestøl, Knut
AU - Schaner, Marci E.
AU - Holm, Ruth
AU - Etemadmoghadam, Dariush
AU - Alsop, Kathryn
AU - Brown, Pat
AU - Mitchell, Gillian
AU - Fereday, Sian
AU - DeFazio, Anna
AU - Bowtell, David D.L.
AU - Kristensen, Gunnar B.
AU - Lingjærde, Ole Christian
AU - Børresen-Dale, Anne Lise
PY - 2013/1/29
Y1 - 2013/1/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872798812&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0054356
DO - 10.1371/journal.pone.0054356
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SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e54356
ER -