Introduction Small cell carcinoma of the ovary, hypercalcemia type (SCCOHT) is a rare and lethal malignancy that occurs most frequently in young women. Studies have shown that mutations in the SMARCA4 gene are one of the factors driving the development of SCCOHT. However, little has been reported about the molecular characteristics in Asian patients. This study aims to reveal the genetic and expression profiles of an independent cohort of Chinese SCCOHT cases by Whole Exome Sequencing (WES) and RNA sequencing.

Methods We enrolled a total of 12 patients with SCCOHT. WES was conducted in 10 of them and 4 were matched with blood samples. We also obtained fresh tumor tissue from 5 patients and performed RNA sequencing.

Results Among the 12 SCCOHT patients, 10 carried SMARCA4 mutations accompanied by loss of protein expression and 1 had a deletion of exon 1–6 in SMARCB1. Somatic variations affecting Notch and Hippo signaling pathway were detected in 60.0% of SCCOHT. Through gene set variation analysis (GSVA), the following pathways were up-regulated in SCCOHT compared with benign ovarian tissue: oxidative phosphorylation, MYC targets, E2F targets, G2M checkpoint, etc. While Notch and WNT signaling pathways were down-regulated.

Conclusion/Implications Here we report the molecular profile of SCCOHT in the Chinese population for the first time. These findings contribute to the further exploration of the pathogenesis of SCCOHT and the development of new targeted therapies.