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Oncotarget. 2017 Nov 15;8(68):112770-112782. doi: 10.18632/oncotarget.22625. eCollection 2017 Dec 22.

The macro-evolutionary events in esophageal squamous cell carcinoma.

Yang B#1,2,3,4, Yan T#1,2,3, Cui H#1,2,3, Xu E#1,2,3,5, Ma Y#1,2,3, Cheng C#1,2,3,6, Zhang L1,2,3, Kong P1,2,3, Wang F1,2,3, Qian Y1,2,3, Yang J1,2,3, Li Y1,2,3,7, Li H1,2,3, Bi Y1,2,3, Hu X1,2,3, Wang J1,2,3, Song B1,2,3, Yang J1,2,3, Gao W1,2,3, Liu J1,8, Zou B1,2,3, Shi R1,2,3, Zhang Y1,8, Liu H1,2,3, Liu Y1,2,3, Zhai Y1,2,3, Chang L1,2,3, Wang Y1,2,3, Zhang Y1,2,3, Jia Z1,2,3, Chen X9, Xi Y5, Li G5, Liang J6, Guo J8, Guo S4, Zhang R4, Cheng X1,2,3, Cui Y1,2,3.

Author information

Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi, China.
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
Department of Pathology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Colorectal & Anal Surgery, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China.
Department of General Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Endoscopy, Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
Contributed equally


Understanding the evolutionary processes operative in cancer genome may provide insights into clinical outcome and drug-resistance. However, studies focus on genomic signatures, especially for macro-evolutionary events, in esophageal squamous cell carcinoma (ESCC) are limited. Here, we integrated published genomic sequencing data to investigate underlying evolutionary characteristics in ESCC. We found most of ESCC genomes were polyploidy with high genomic instability. Whole genome doubling that acts as one of mechanisms for polyploidy was predicted as a late event in the majority of ESCC genome. Moreover, loss of heterozygosity events were more likely to occur in chromosomes harboring tumor suppressor genes in ESCC. The 40% of neutral loss of heterozygosity events was not a result of genome doubling, suggesting an alternative mechanism for neutral loss of heterozygosity formation. Importantly, deconstruction of copy number alterations extending to telomere revealed that telomere-bounded copy number alterations play a critical role for amplification/deletion of oncogenes/suppressor genes. For well-known genes SOX2, PIK3CA and TERT, nearly all of their amplifications were telomere bounded, which was further confirmed in a Japanese ESCC cohort. Furthermore, we provide evidence that karyotype evolution was mostly punctuated in ESCC. Collectively, our data reveal the potential biological role of whole genome doubling, neutral loss of heterozygosity and telomere-bounded copy number alterations, and highlight mecro-evolution in ESCC tumorigenesis.


esophageal squamous cell carcinoma (ESCC); genome evolution; neutral loss of heterozygosity (NLOH); telomere-bounded copy number alterations (TCNAs); whole genome doubling (WGD)

Conflict of interest statement

CONFLICTS OF INTEREST The authors have declared that no conflicts of intrest exist.

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