Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis

Hai De Qin; Xiao Yu Liao; Yuan Bin Chen; Shao Yi Huang; Wen Qiong Xue; Fang Fang Li; Xiao Song Ge; De Qing Liu; Qiuyin Cai; Jirong Long; Xi Zhao Li; Ye Zhu Hu; Shao Dan Zhang; Lan Jun Zhang; Benjamin Lehrman; Alan F. Scott; Dongxin Lin; Yi Xin Zeng; Yin Yao Shugart; Wei Hua Jia

doi:10.1016/j.ajhg.2016.02.021

Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis

Hai De Qin, Xiao Yu Liao, Yuan Bin Chen, Shao Yi Huang, Wen Qiong Xue, Fang Fang Li, Xiao Song Ge, De Qing Liu, Qiuyin Cai, Jirong Long, Xi Zhao Li, Ye Zhu Hu, Shao Dan Zhang, Lan Jun Zhang, Benjamin Lehrman, Alan F. Scott, Dongxin Lin, Yi Xin Zeng, Yin Yao Shugart, Wei Hua Jia

School of Medicine

Research output: Contribution to journal › Article › peer-review

75 Scopus citations

Abstract

The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.

Original language	English (US)
Pages (from-to)	709-727
Number of pages	19
Journal	American journal of human genetics
Volume	98
Issue number	4
DOIs	https://doi.org/10.1016/j.ajhg.2016.02.021
State	Published - Apr 7 2016

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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Qin, H. D., Liao, X. Y., Chen, Y. B., Huang, S. Y., Xue, W. Q., Li, F. F., Ge, X. S., Liu, D. Q., Cai, Q., Long, J., Li, X. Z., Hu, Y. Z., Zhang, S. D., Zhang, L. J., Lehrman, B., Scott, A. F., Lin, D., Zeng, Y. X., Shugart, Y. Y., & Jia, W. H. (2016). Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis. American journal of human genetics, 98(4), 709-727. https://doi.org/10.1016/j.ajhg.2016.02.021

Qin, HD, Liao, XY, Chen, YB, Huang, SY, Xue, WQ, Li, FF, Ge, XS, Liu, DQ, Cai, Q, Long, J, Li, XZ, Hu, YZ, Zhang, SD, Zhang, LJ, Lehrman, B, Scott, AF, Lin, D, Zeng, YX, Shugart, YY & Jia, WH 2016, 'Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis', American journal of human genetics, vol. 98, no. 4, pp. 709-727. https://doi.org/10.1016/j.ajhg.2016.02.021

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title = "Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis",

abstract = "The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.",

author = "Qin, {Hai De} and Liao, {Xiao Yu} and Chen, {Yuan Bin} and Huang, {Shao Yi} and Xue, {Wen Qiong} and Li, {Fang Fang} and Ge, {Xiao Song} and Liu, {De Qing} and Qiuyin Cai and Jirong Long and Li, {Xi Zhao} and Hu, {Ye Zhu} and Zhang, {Shao Dan} and Zhang, {Lan Jun} and Benjamin Lehrman and Scott, {Alan F.} and Dongxin Lin and Zeng, {Yi Xin} and Shugart, {Yin Yao} and Jia, {Wei Hua}",

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doi = "10.1016/j.ajhg.2016.02.021",

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AU - Qin, Hai De

AU - Liao, Xiao Yu

AU - Chen, Yuan Bin

AU - Huang, Shao Yi

AU - Xue, Wen Qiong

AU - Li, Fang Fang

AU - Ge, Xiao Song

AU - Liu, De Qing

AU - Cai, Qiuyin

AU - Long, Jirong

AU - Li, Xi Zhao

AU - Hu, Ye Zhu

AU - Zhang, Shao Dan

AU - Zhang, Lan Jun

AU - Lehrman, Benjamin

AU - Scott, Alan F.

AU - Lin, Dongxin

AU - Zeng, Yi Xin

AU - Shugart, Yin Yao

AU - Jia, Wei Hua

PY - 2016/4/7

Y1 - 2016/4/7

N2 - The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.

AB - The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.

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Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis

Abstract

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