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Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance

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  • Xuan Zong

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ying Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xinxin Peng

    (Precision Scientific (Beijing) Co., Ltd.)

  • Dongyan Cao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Mei Yu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jinhui Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Hongyue Li

    (Precision Scientific (Beijing) Co., Ltd.)

  • Xuejiao Guo

    (Precision Scientific (Beijing) Co., Ltd.)

  • Han Liang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jiaxin Yang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.

Suggested Citation

  • Xuan Zong & Ying Zhang & Xinxin Peng & Dongyan Cao & Mei Yu & Jinhui Wang & Hongyue Li & Xuejiao Guo & Han Liang & Jiaxin Yang, 2021. "Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23681-0
    DOI: 10.1038/s41467-021-23681-0
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