The genomic complexity and heterogeneity of high-grade serous ovarian cancer (HGSOC) has hampered the realisation of successful therapies and effective personalised treatment is an unmet clinical need. Here we show that primary HGSOC spheroid models can be used to predict drug response and use them to demonstrate that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and drug response. These genes are often located in areas of the genome with frequent clonal SCNAs. MYC chromosomal copy number is associated with ex-vivo and clinical response to paclitaxel and ex-vivo response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context to MYC-amplified HGSOC is mostly due to increased prevalence of SCNAs in genes from the PI3K pathway. These results suggest that SCNAs encompassing driver genes could be used to inform therapeutic response in the context of clinical trials testing personalised medicines.

中文翻译：

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影响驱动基因的体细胞染色体数目改变告知高级浆液性卵巢癌的体外和临床药物反应

高度浆液性卵巢癌（HGSOC）的基因组复杂性和异质性阻碍了成功疗法的实现，有效的个性化治疗是临床上尚未满足的需求。在这里，我们显示了主要的HGSOC椭球模型可用于预测药物反应，并使用它们来证明频繁扩增的HGSOC癌症基因中的体细胞拷贝数变化（SCNA）与基因表达和药物反应显着相关。这些基因通常位于具有频繁克隆SCNA的基因组区域。MYC染色体拷贝数与对紫杉醇的体外和临床反应以及对mTORC1 / 2抑制的体外反应有关。在MYC扩增的HGSOC中，mTOR生存途径的激活主要是由于来自PI3K途径的基因中SCNA的患病率增加。