Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

Xue-Ke Zhao, Pengwei Xing, Xin Song, Miao Zhao, Linxuan Zhao, Yonglong Dang, Ling-Ling Lei, Rui-Hua Xu, Wen-Li Han, Pan-Pan Wang, Miao-Miao Yang, Jing-Feng Hu, Kan Zhong, Fu-You Zhou, Xue-Na Han, Chao-Long Meng, Jia-Jia Ji, Xingqi Chen () and Li-Dong Wang ()
Additional contact information
Xue-Ke Zhao: Zhengzhou University
Pengwei Xing: Uppsala University
Xin Song: Zhengzhou University
Miao Zhao: Uppsala University
Linxuan Zhao: Uppsala University
Yonglong Dang: Uppsala University
Ling-Ling Lei: Zhengzhou University
Rui-Hua Xu: Zhengzhou University
Wen-Li Han: Zhengzhou University
Pan-Pan Wang: Zhengzhou University
Miao-Miao Yang: Zhengzhou University
Jing-Feng Hu: Zhengzhou University
Kan Zhong: Zhengzhou University
Fu-You Zhou: Zhengzhou University
Xue-Na Han: Zhengzhou University
Chao-Long Meng: Zhengzhou University
Jia-Jia Ji: Zhengzhou University
Xingqi Chen: Uppsala University
Li-Dong Wang: Zhengzhou University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.

Date: 2021
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DOI: 10.1038/s41467-021-26745-3

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