Parallel evolution of tumour subclones mimics diversity between tumours
Parallel evolution of tumour subclones mimics diversity between tumours
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DOI：
10.1002/path.4214
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发表时间：
2013-08-01
影响因子：
7.3
通讯作者：
Swanton, Charles
中科院分区：
文献类型：
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作者：
Martinez, Pierre;Birkbak, Nicolai Juul;Swanton, Charles
瘤内异质性（ITH）可能会促进肿瘤适应性，并损害个性化医疗方法的疗效。肿瘤内异质性（肿瘤内异质性）相对于肿瘤间遗传差异（肿瘤间异质性）的规模尚不清楚。为了解决这个问题，我们从8个III期和IV期透明细胞肾细胞癌（ccRCC）中获得了48个活检组织，并使用DNA拷贝数分析将来自同一肿瘤的活检组织与来自癌症基因组图谱（TCGA）的440个单一肿瘤活检组织进行比较。TCGA和多区域ccRCC样本的无监督分层聚类显示，来自相同肿瘤的样本分离成不相关的聚类; 25%的多区域样本与来自相同肿瘤的任何其他样本相比，与不相关样本更相似。我们发现，单次活检中大多数复发性DNA拷贝数驱动畸变在晚期ccRCC中并不普遍存在，并且可能代表肿瘤进展期间获得的亚克隆事件。个体肿瘤内的这种异质性亚克隆遗传改变可能会损害通过不同拷贝数改变和临床结果分类的稳健ccRCC分子亚型的鉴定。个体肿瘤不同区域中不同亚克隆拷贝数事件的共存反映了个体ccRCC通过多种进化途径的多样化，并可能导致肿瘤采样偏倚和对肿瘤进展和临床结果的影响。版权所有（c）2013大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.