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

Xuan Zong, Ying Zhang, Xinxin Peng, Dongyan Cao, Mei Yu, Jinhui Wang, Hongyue Li, Xuejiao Guo, Han Liang () and Jiaxin Yang ()
Additional contact information
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
Jiaxin Yang: Chinese Academy of Medical Sciences and Peking Union Medical College

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

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23681-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23681-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23681-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().