Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma.
Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma.
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DOI：
10.1038/onc.2010.245
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发表时间：
2010-09-02
期刊：
影响因子：
8
通讯作者：
Brenton, J. D.
中科院分区：
文献类型：
--
作者：
Cooke, S. L.;Ng, C. K. Y.;Melnyk, N.;Garcia, M. J.;Hardcastle, T.;Temple, J.;Langdon, S.;Huntsman, D.;Brenton, J. D.
卵巢癌的化疗耐药性知之甚少。癌症的进化模型预测，在治疗后，由于内在抗性亚克隆的生长，或者在治疗的选择压力下在残留疾病中进化，出现抗性。为了研究高级别浆液性（HGS）卵巢癌的遗传进化，我们首先分析了铂类耐药发生前后三例HGS癌的细胞系系列（PEO 1、PEO 4和PEO 6、PEA 1和PEA 2以及PEO 14和PEO 23）。用24色荧光原位杂交和SNP阵列比较基因组杂交（CGH）分析显示，在同一个体的不同时间点存在的克隆中存在互斥的核内复制和杂合性丢失事件。这意味着铂敏感性和耐药性疾病不是线性相关的，而是在肿瘤发展的早期阶段共享共同的祖先。来自CTCR-OV 01临床研究的6个配对的新辅助治疗前和后HGS样品的阵列CGH分析未显示广泛的拷贝数差异，表明一个克隆在呈现时是强显性的。这些数据表明，HGS癌中的顺铂耐药性是从预先存在的次要克隆发展而来的，但这些克隆的富集在短期化疗治疗期间并不明显。
Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either due to outgrowth of an intrinsically resistant sub-clone, or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6, PEA1 and PEA2, and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and SNP array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different timepoints in the same individual. This implies that platinum sensitive and resistant disease was not linearly related but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment.
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影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
DOI：
10.1038/nrc2644
发表时间：
2009-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
4.8
作者：
Roschke, AV;Stover, K;Kirsch, IR
通讯作者：
Kirsch, IR
影响因子：
45.3
作者：
MARKMAN, M;ROTHMAN, R;LEWIS, JL
通讯作者：
LEWIS, JL
影响因子：
11.5
作者：
Herzog, TJ
通讯作者：
Herzog, TJ