摘要
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 heterogene-ity 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 devel-opment 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 docu-ment, 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. Copyright a 2016 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
