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- Title
Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets.
- Authors
Lu, Jun; Ding, Yongfeng; Chen, Yanyan; Jiang, Junjie; Chen, Yiran; Huang, Yingying; Wu, Mengjie; Li, Chengzhi; Kong, Mei; Zhao, Wenyi; Wang, Haohao; Zhang, Jing; Li, Zhongqi; Lu, Yimin; Yu, Xiongfei; Jin, Ketao; Zhou, Donghui; Zhou, Tianhua; Teng, Fei; Zhang, Haibin
- 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. Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.
- Subjects
DRUG target; STOMACH cancer; ALPHA fetoproteins; THERAPEUTICS; PROGNOSIS; EXOMES; GENE amplification
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-24170-0