Centre for Evolution and Cancer, The Institute of Cancer Research, London SM2 5NG, UK.
Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, 24306 Plön, Germany.
Sci Rep. 2017 Mar 27;7:44991. doi: 10.1038/srep44991.
Modern cancer therapies aim at targeting tumour-specific alterations, such as mutations or neo-antigens, and maximal treatment efficacy requires that targeted alterations are present in all tumour cells. Currently, treatment decisions are based on one or a few samples per tumour, creating uncertainty on whether alterations found in those samples are actually present in all tumour cells. The probability of classifying clonal versus sub-clonal alterations from multi-region profiling of tumours depends on the earliest phylogenetic branching event during tumour growth. By analysing 181 samples from 10 renal carcinoma and 11 colorectal cancers we demonstrate that the information gain from additional sampling falls onto a simple universal curve. We found that in colorectal cancers, 30% of alterations identified as clonal with one biopsy proved sub-clonal when 8 samples were considered. The probability to overestimate clonal alterations fell below 1% in 7/11 patients with 8 samples per tumour. In renal cell carcinoma, 8 samples reduced the list of clonal alterations by 40% with respect to a single biopsy. The probability to overestimate clonal alterations remained as high as 92% in 7/10 renal cancer patients. Furthermore, treatment was associated with more unbalanced tumour phylogenetic trees, suggesting the need of denser sampling of tumours at relapse.
现代癌症疗法旨在针对肿瘤特异性改变，如突变或新抗原，并且最大的治疗效果要求靶向改变存在于所有肿瘤细胞中。目前，治疗决策基于每个肿瘤的一个或几个样本，这使得我们不确定在这些样本中发现的改变实际上是否存在于所有肿瘤细胞中。从肿瘤的多区域分析中对克隆与亚克隆改变进行分类的概率取决于肿瘤生长过程中最早的系统发育分支事件。通过分析来自 10 例肾细胞癌和 11 例结直肠癌的 181 个样本，我们证明了从额外采样中获得的信息增益遵循一个简单的通用曲线。我们发现，在结直肠癌中，当考虑 8 个样本时，1 个活检确定为克隆的 30%的改变被证明为亚克隆。当每个肿瘤有 8 个样本时，7/11 名患者高估克隆改变的概率低于 1%。在肾细胞癌中，与单个活检相比，8 个样本将克隆改变的数量减少了 40%。在 7/10 的肾癌细胞癌患者中，高估克隆改变的概率仍然高达 92%。此外，治疗与更不平衡的肿瘤系统发育树相关，这表明需要在肿瘤复发时更密集地采样。
