Analysis of the Genomic Landscape of Yolk Sac Tumors Reveals Mechanisms of Evolution and Chemoresistance

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jun 12

PMID 34117242

Citations 3

Authors

Xuan Zong

Ying Zhang

Xinxin Peng

Dongyan Cao

Mei Yu

Jinhui Wang

Hongyue Li

Xuejiao Guo

Han Liang

Jiaxin Yang

Affiliations

Soon will be listed here.

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.

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