Nat Genet:科学家发现相同肿瘤中存在不同遗传复杂性的癌细胞

Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma

近日，一项刊登于国际杂志Namre Genetics上的研究报告中。来自美国洛杉矶希达-西奈（Cedars-Sinai）医学院的研究人员通过研究在食管肿瘤的组织样本中鉴别出了2000多个基因突变，从而详细阐述了癌症的复杂性。本文研究表明。单一肿瘤的不同区域或许具有多种遗传模式。

Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others. By contrast, the majority of truncal and clonal driver mutations occurred in tumor-suppressor genes, including TP53, KMT2D and ZNF750, among others. Interestingly, phyloepigenetic trees robustly recapitulated the topological structures of the phylogenetic trees, indicating a possible relationship between genetic and epigenetic alterations. Our integrated investigations of spatial ITH and clonal evolution provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ESCC.