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

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  • 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)

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.

Suggested Citation

  • 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 & Xu, 2021. "Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26745-3
    DOI: 10.1038/s41467-021-26745-3
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