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PLoS One. 2013;8(1):e54356. doi: 10.1371/journal.pone.0054356. Epub 2013 Jan 23.

High levels of genomic aberrations in serous ovarian cancers are associated with better survival.

Collaborators (275)

Bowtell D, Chenevix-Trench G, Green A, Webb P, deFazio A, Gertig D, Traficante N, Moore S, Hung J, Fereday S, Harrap K, Sadkowsky T, Pandeya N, Malt M, Mellon A, Robertson R, Vanden Bergh T, Jones M, Mackenzie P, Maidens J, Nattress K, Chiew YE, Stenlake A, Sullivan H, Alexander B, Ashover P, Brown S, Corrish T, Green L, Jackman L, Ferguson K, Martin K, Martyn A, Ranieri B, White J, Jayde V, Bowes L, Mamers P, Galletta L, Giles D, Hendley J, Alsop K, Schmidt T, Shirley H, Ball C, Young C, Viduka S, Tran H, Bilic S, Glavinas L, Brooks J, Stuart-Harris R, Kirsten F, Rutovitz J, Clingan P, Glasgow A, Proietto A, Braye S, Otton G, Shannon J, Bonaventura T, Stewart J, Begbie S, Friedlander M, Bell D, Baron-Hay S, Ferrier A, Gard G, Nevell D, Pavlakis N, Valmadre S, Young B, Camaris C, Crouch R, Edwards L, Hacker N, Marsden D, Robertson G, Beale P, Beith J, Carter J, Dalrymple C, Houghton R, Russell P, Anderson L, Links M, Grygiel J, Hill J, Brand A, Byth K, Jaworski R, Harnett P, Sharma R, Wain G, Ward B, Papadimos D, Crandon A, Cummings M, Horwood K, Obermair A, Perrin L, Wyld D, Nicklin J, Davy M, Oehler MK, Hall C, Dodd T, Healy T, Pittman K, Henderson D, Miller J, Pierdes J, Achan A, Blomfield P, Challis D, McIntosh R, Parker A, Brown B, Rome R, Allen D, Grant P, Hyde S, Robbie RL, Healy D, Jobling T, Manolitsas T, McNealage J, Rogers P, Susil B, Sumithran E, Simpson I, Phillips K, Rischin D, Fox S, Johnson D, Waring P, Lade S, Loughrey M, O'Callaghan N, Murray W, Mileshkin L, Allan P, Billson V, Pyman J, Neesham D, Quinn M, Hamilton A, Underhill C, Bell R, Ng LF, Blum R, Ganju V, Hammond I, Leung Y, McCartney A, Stewart C, Buck M, Haviv I, Purdie D, Whiteman D, Zeps N, Gurry P, Hamilton A, Hankinson S, Meltzer P, Stuart-Harris R, Kirsten F, Rutovitz J, Clingan P, Glasgow A, Proietto A, Braye S, Otton G, Shannon J, Bonaventura T, Stewart J, Begbie S, Friedlander M, Bell D, Baron-Hay S, Ferrier A, Gard G, Nevell D, Pavlakis N, Valmadre S, Young B, Camaris C, Crouch R, Edwards L, Hacker N, Marsden D, Robertson G, Beale P, Beith J, Carter J, Dalrymple C, Houghton R, Russell P, Anderson L, Links M, Grygiel J, Hill J, Brand A, Byth K, Jaworski R, Harnett P, Sharma R, Wain G, Purdie D, Whiteman D, Ward B, Papadimos D, Crandon A, Cummings M, Horwood K, Obermair A, Perrin L, Wyld D, Nicklin J, Davy M, Oehler MK, Hall C, Dodd T, Healy T, Pittman K, Henderson D, Miller J, Pierdes J, Achan A, Blomfield P, Challis D, McIntosh R, Parker A, Brown B, Rome R, Allen D, Grant P, Hyde S, Robbie RL, Healy D, Jobling T, Manolitsas T, McNealage J, Rogers P, Susil B, Sumithran E, Simpson I, Haviv I, Phillips K, Rischin D, Fox S, Johnson D, Lade S, Waring P, Loughrey M, O'Callaghan N, Murray B, Mileshkin L, Allan P, Billson V, Pyman J, Neesham D, Quinn M, Hamilton A, Underhill C, Bell R, Ng LF, Blum R, Ganju V, Hammond I, McCartney A, Stewart C, Leung Y, Buck M, Zeps N.

Author information

1
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. lars.o.baumbusch@rr-research.no

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.

PMID:
23372714
PMCID:
PMC3553118
DOI:
10.1371/journal.pone.0054356
[Indexed for MEDLINE]
Free PMC Article
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