Intratumoral Genomic Heterogeneity May Hinder Precision Medicine Strategies in Patients with Serous Ovarian Carcinoma
Intratumoral Genomic Heterogeneity May Hinder Precision Medicine Strategies in Patients with Serous Ovarian Carcinoma
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DOI：
10.3390/diagnostics10040200
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发表时间：
2020-04-01
期刊：
影响因子：
3.6
通讯作者：
Nishihara, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakamura, Kohei;Aimono, Eriko;Nishihara, Hiroshi
包括全面基因组测序在内的精准医学是治疗高级别浆液性癌（HGSC）的潜在治疗选择。然而，HGSC在结构、细胞和分子水平上是异质性肿瘤。肿瘤内的分子异质性目前限制了基于基因突变状态的医疗策略的精确性。本研究分析了HGSC患者中具有不同病理特征的三个组织区域中160种癌症相关遗传改变的存在。患者表现出不同程度的大的非典型细胞和促纤维增生反应的组织学异质性特征。TP53突变、ERBB2和KRAS扩增以及WT1、CDH1和KDM6A缺失被检测为可操作的基因改变。有趣的是，ERBB2和KRAS扩增状态根据检查的区域逐渐改变。这种差异与病理特征的差异相一致。我们的研究结果表明，在制定精确的肿瘤学策略之前，需要对显示病理特征进展的适当组织区域进行采样，以进行分子分析，从而解决与肿瘤异质性相关的问题。
Precision medicine, which includes comprehensive genome sequencing, is a potential therapeutic option for treating high-grade serous carcinoma (HGSC). However, HGSC is a heterogeneous tumor at the architectural, cellular, and molecular levels. Intratumoral molecular heterogeneity currently limits the precision of medical strategies based on the gene mutation status. This study was carried out to analyze the presence of 160 cancer-related genetic alterations in three tissue regions with different pathological features in a patient with HGSC. The patient exhibited histological heterogeneous features with different degrees of large atypical cells and desmoplastic reactions. TP53 mutation, ERBB2 and KRAS amplification, and WT1, CDH1, and KDM6A loss were detected as actionable gene alterations. Interestingly, the ERBB2 and KRAS amplification status gradually changed according to the region examined. The difference was consistent with the differences in pathological features. Our results demonstrate the need for sampling of the appropriate tissue region showing progression of pathological features for molecular analysis to solve issues related to tumor heterogeneity prior to developing precision oncology strategies.