Clinical Characteristics and Mutation Analyses of Ovarian Sertoli-Leydig Cell Tumors

The oncologist

article

Zhen Yuan¹  Huimei Zhou¹  Yao Wang¹  Xiao Huo¹  Dezhi Jiang²  Mei Yu¹  Dongyan Cao¹  Huanwen Wu³  Keng Shen¹  Jiaxin Yang¹  Ying Zhang¹ 

[1] Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences;Department of Bioinformatics;Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences

关键词: DICER1;    Germline mutations;    Somatic mutations;    Sertoli-Leydig cell tumors;    Whole exome sequencing;   

DOI  :  10.1634/theoncologist.2020-0110

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background There are limited studies on Sertoli-Leydig cell tumors (SLCTs) and no data in the population of Chinese patients with SLCTs from the genetic level. In addition, previous studies on SLCTs have focused exclusively on mutations in the DICER1 gene and no data exists on the genetic landscape of SLCTs. Methods Patients with moderately or poorly differentiated SLCTs who underwent surgical resection between January 2012 and October 2018 in our institution were recruited. Whole exome sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue and peripheral blood or normal tissue samples. Results Seventeen patients were recruited with 19 tumor samples. The rate of tumor-associated germline mutations was 6 of 17 (35.3%), and that of DICER1 germline mutations was 4 of 17 (23.5%). Regarding clinical relapse, patients with germline tumor-associated mutations had significantly poorer prognosis than those without ( p  = .007), and those with germline DICER1 mutations were relatively more likely to exhibit clinical relapse, although not to a significant degree ( p  = .069). Regarding somatic mutations, firstly, the subclone evolution analysis demonstrated that the two tumors on the contralateral ovary were primary tumors, respectively. Secondly, somatic mutations were most commonly found in CDC27 (10/19, 52.6%), DICER1 (4/19, 21.1%), and MUC22 (4/19, 21.1%). And the analysis of cancer cell fractions showed that DICER1 mutations were correlated with tumorigenesis of SLCTs. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients ( p  = .022 and p  = .001, respectively). Conclusion Our study indicates that genetic testing may have important clinical significance for patients with SLCTs, particularly for younger patients. Implications for Practice Bilateral ovarian Sertoli-Leydig cell tumors were verified to be primary tumors from the genetic perspective. The rates of germline and somatic DICER1 mutations were 4 of 17 (23.5%) and 4 of 19 (21.1%), respectively. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients ( p  = .022 and p  = .001, respectively).

【 授权许可】

CC BY|CC BY-NC