GRCh38 · COSMIC v99


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Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma.
Paper ID
Hao JJ, Lin DC, Dinh HQ, Mayakonda A, Jiang YY, Chang C, Jiang Y, Lu CC, Shi ZZ, Xu X, Zhang Y, Cai Y, Wang JW, Zhan QM, Wei WQ, Berman BP, Wang MR and Koeffler HP
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nature genetics, 2016;48(12):1500-1507
ISSN: 1546-1718
PMID: 27749841 (view at PubMed or Europe PMC)
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.
Paper Status