Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets

Jun Lu, Yongfeng Ding, Yanyan Chen, Junjie Jiang, Yiran Chen, Yingying Huang, Mengjie Wu, Chengzhi Li, Mei Kong, Wenyi Zhao, Haohao Wang, Jing Zhang, Zhongqi Li, Yimin Lu, Xiongfei Yu, Ketao Jin, Donghui Zhou, Tianhua Zhou, Fei Teng, Haibin Zhang, Zhan Zhou (), Haiyong Wang () and Lisong Teng ()
Additional contact information
Jun Lu: Zhejiang University
Yongfeng Ding: Zhejiang University
Yanyan Chen: Zhejiang University
Junjie Jiang: Zhejiang University
Yiran Chen: Zhejiang University
Yingying Huang: Zhejiang University
Mengjie Wu: Zhejiang University
Chengzhi Li: Zhejiang University
Mei Kong: Zhejiang University
Wenyi Zhao: College of Pharmaceutical Sciences and Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Zhejiang University
Haohao Wang: Zhejiang University
Jing Zhang: Zhejiang University
Zhongqi Li: Zhejiang University
Yimin Lu: Zhejiang University
Xiongfei Yu: Zhejiang University
Ketao Jin: Zhejiang University
Donghui Zhou: Zhejiang University
Tianhua Zhou: Cancer center, Zhejiang University
Fei Teng: Hangzhou Oncocare Co. Ltd
Haibin Zhang: Zhejiang University
Zhan Zhou: College of Pharmaceutical Sciences and Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Zhejiang University
Haiyong Wang: Zhejiang University
Lisong Teng: Zhejiang University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer. However, little is known about the genomic features of this disease. We perform whole-exome sequencing analysis of AFPGC, and identify 34 significantly mutated genes. Somatic copy number alterations analysis reveals several significant focal amplifications (e.g. 19q12, 17q12) and focal deletions (e.g. 1p36.11, 9p21.3), and some of these negatively affect the patient prognosis. Comparative analyses reveal that AFPGC has distinct genomic features from gastric cancer of The Cancer Genome Atlas as well as four molecular subtypes. Several frequently altered genes with potential as therapeutic targets are identified in AFPGC. Further analysis reveals that AFPGC with amplification of CCNE1 at 19q12 and/or ERBB2 at 17q12 show poorer survival and more aggressive. Subsequently, based on our established patient-derived xenograft models for AFPGC, translational research is performed and the therapeutic value of targeting CCNE1 and ERBB2 is validated. In this work, we provide an understanding of genomic characteristics of AFPGC and propose a platform to explore and validate the genome-guided personalized treatment for this disease.

Date: 2021
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DOI: 10.1038/s41467-021-24170-0

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