Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
PLoS One. 2013;8(1):e54356. doi: 10.1371/journal.pone.0054356. Epub 2013 Jan 23.
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.
基因组不稳定性和癌症中的拷贝数改变通常与预后不良有关;然而,最近的研究表明,极端水平的基因组异常可能对特定肿瘤类型患者的生存结果有益。我们使用分别在挪威(n=74)和澳大利亚(n=70)生成的两个独立数据集,研究了主要为高级别浆液性卵巢癌(SOC)的基因组不稳定性程度。基因组不稳定性通过总畸变指数(TAI)来量化,TAI 是衡量肿瘤中拷贝数变化的丰度和基因组大小的指标。在挪威队列中,TAI 高于中位数的患者总生存期(p<0.001)和无进展生存期(p<0.05)显著延长。在澳大利亚队列中,TAI 高于中位数的患者总生存期延长(p<0.05),但无进展生存期适度延长,但无统计学意义。TAI 作为连续变量的单变量和多变量 Cox 回归分析证实了这些结果。我们的结果提供了进一步的证据,支持高水平的基因组不稳定性与高级别 SOC 患者的生存延长之间存在关联,可能是因为受损的基因组完整性可能导致对化疗药物的敏感性增加。