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

被引：19

作者：

Baumbusch, Lars O. ^{[1
]}

Helland, Aslaug ^{[1
,2
,3
]}

Wang, Yun ^{[1
,4
]}

Liestol, Knut ^{[5
,6
]}

Schaner, Marci E. ^{[7
]}

Holm, Ruth ^{[8
]}

Etemadmoghadam, Dariush ^{[9
,10
,11
]}

Alsop, Kathryn ^{[9
,10
]}

Brown, Pat ^{[7
]}

Mitchell, Gillian ^{[9
,10
]}

Fereday, Sian ^{[9
]}

DeFazio, Anna ^{[12
,13
]}

Bowtell, David D. L. ^{[9
,10
,11
,14
]}

Kristensen, Gunnar B. ^{[4
,15
]}

Lingjaerde, Ole Christian ^{[1
,5
,6
]}

Borresen-Dale, Anne-Lise ^{[1
,3
]}

机构：

[1] Norwegian Radium Hosp, Inst Canc Res, Dept Genet, Oslo Univ Hosp, Oslo, Norway

[2] Norwegian Radium Hosp, Dept Oncol, Oslo Univ Hosp, Oslo, Norway

[3] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway

[4] Norwegian Radium Hosp, Dept Gynecol Oncol, Oslo Univ Hosp, Oslo, Norway

[5] Univ Oslo, Dept Informat, Biomed Informat Grp, N-0316 Oslo, Norway

[6] Univ Oslo, Ctr Canc Biomed, Oslo, Norway

[7] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA

[8] Norwegian Radium Hosp, Dept Pathol, Oslo Univ Hosp, Oslo, Norway

[9] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[10] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[11] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia

[12] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia

[13] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia

[14] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic, Australia

[15] Norwegian Radium Hosp, Inst Med Informat, Oslo Univ Hosp, Oslo, Norway

来源：

PLOS ONE | 2013年 / 8卷 / 01期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

LONG-TERM SURVIVAL; CHROMOSOMAL INSTABILITY; GENE-EXPRESSION; COPY NUMBER; HYBRIDIZATION; BREAST; SEGREGATION; SENSITIVITY; MECHANISMS; PHENOTYPE;

D O I：

10.1371/journal.pone.0054356

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

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