Clinical Characteristics and Mutation Analyses of Ovarian Sertoli‐Leydig Cell Tumors. (11th August 2020)

• Record Type: Journal Article
• Authors: Yuan, Zhen; Huo, Xiao; Jiang, Dezhi; Yu, Mei; Cao, Dongyan; Wu, Huanwen; Shen, Keng; Yang, Jiaxin; Zhang, Ying; Zhou, Huimei; Wang, Yao
• Is Part Of: Oncologist. Volume 25:Number 9(2020)
• Page Start: e1396
• Page End: e1405
• Publication Date: 2020-08-11
• Subjects: DICER1 -- Germline mutations -- Somatic mutations -- Sertoli‐Leydig cell tumors -- Whole exome sequencing; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2020-0110
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: 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). Abstract : In this study, whole exome sequencing was conducted on tumor samples and paired germline samples from patients with Sertoli‐Leydig cell tumors to explore not only DICER1 mutations for Chinese populations but also other genetic variations related to pathogenesis and prognosis, which could lay a preliminary foundation for genetic counseling.