Clinical Characteristics and Mutation Analysis of Ovarian Sertoli-Leydig Cell Tumors.

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 ofDICER1germline 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 germlineDICER1mutations 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 inCDC27(10/19, 52.6%),DICER1(4/19, 21.1%), andMUC22(4/19, 21.1%). And the analysis of cancer cell fractions showed thatDICER1mutations were correlated with tumorigenesis of SLCTs. The rates of germline and somaticDICER1mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 andp = .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 somaticDICER1mutations were 4 of 17 (23.5%) and 4 of 19 (21.1%), respectively. The rates of germline and somaticDICER1mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 andp = .001, respectively).