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 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.
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. lars.o.baumbusch@rr-research.no
Lars O
LO
Baumbusch
Åslaug
Å
Helland
Yun
Y
Wang
Knut
K
Liestøl
Marci E
ME
Schaner
Ruth
R
Holm
Dariush
D
Etemadmoghadam
Kathryn
K
Alsop
Pat
P
Brown
Gillian
G
Mitchell
Sian
S
Fereday
Anna
A
DeFazio
David D L
DD
Bowtell
Gunnar B
GB
Kristensen
Ole Christian
OC
Lingjærde
Anne-Lise
AL
Børresen-Dale
D000328:Adult; D002869:Chromosome Aberrations; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D018293:Cystadenoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D056915:DNA Copy Number Variations; D005260:Female; D016678:Genome; D042822:Genomic Instability; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis