Intra-tumor heterogeneity in head and neck cancer and its clinical implications.
Intra-tumor heterogeneity in head and neck cancer and its clinical implications.
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DOI：
10.1016/j.wjorl.2016.05.007
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Rocco JW
中科院分区：
文献类型：
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作者：
Mroz EA;Rocco JW
长期以来，肿瘤内癌细胞之间存在的可遗传差异，称为肿瘤内遗传异质性，一直被怀疑在治疗反应差的原因中发挥了作用。过去十年的研究已经证明了个体患者肿瘤中存在这种异质性，并证明了其潜在的临床意义。然而，识别这种异质性的研究方法并不容易适应广泛的临床应用。在简要回顾了这一背景之后，我们描述了一种基于单个肿瘤样本的全外显子测序的肿瘤内遗传异质性的测量方法的发展，该方法可以应用于临床环境中的活组织标本。这一方法现在已被用于头颈部鳞状细胞癌(HNSCC)，在一项大型的多机构研究中首次证明了高肿瘤内遗传异质性与较短的总生存期之间的关系。因此，现在需要解决异质性对研究和临床护理的影响。
The presence of heritable differences among cancer cells within a tumor, called intra-tumor genetic heterogeneity, has long been suspected of playing a role in poor responses to therapy. Research over the past decade has documented the existence of such heterogeneity within tumors of individual patients and documented its potential clinical significance. The research methods for identifying this heterogeneity were not, however, readily adaptable to widespread clinical application. After a brief review of this background, we describe the development of a measure of intra-tumor genetic heterogeneity, based on whole-exome sequencing of individual tumor samples, that could be applied to biopsy specimens in a clinical setting. This measure has now been used in head and neck squamous cell carcinoma (HNSCC) to document, for the first time, a relation of high intra-tumor genetic heterogeneity to shorter overall survival in a large, multi-institutional study. The implications of heterogeneity for research and clinical care thus now need to be addressed.