Distinct molecular features of ovarian adult granulosa cell tumors and co-occurring primary malignancies–an exploratory case series

Background: Ovarian adult granulosa cell tumor (aGCT) is a rare gynecological malignancy and has been associated with increased incidence of other primary malignancies, particularly endometrial. However, potential shared molecular features in these tumors remain poorly understood. This study aimed to use Next Generation Sequencing to explore molecular alterations between aGCT and co-occurring breast, colon, and endometrial cancers within the same patients. Methods: Female individuals diagnosed with aGCT and a synchronous endometrial cancer, or with a history of breast, or colorectal cancer from 1980 to 2022 were identified using the Danish Pathology Registry. Clinical and histopathological characteristics were reviewed for each case, and Next Generation Sequencing was performed on tumor DNA from both the aGCT and the other primary cancer using the Oncomine Comprehensive Assay Plus. Results: We included 15 individuals diagnosed with aGCT and a history of other primary malignancies originating from the endometrium, breast, or colorectum. Between 1982 and 2022, the series included five patients with synchronous endometrial cancer, five with a history of breast cancer, three with a history of colorectal cancer, one with both breast and endometrial cancer, and one with both breast and colorectal cancer. No shared somatic alterations were identified between the aGCTs and the other malignancies. Conclusion: No shared somatic alterations were detected using the Oncomine Comprehensive Assay Plus panel. This suggests that co-occurrence of aGCT with endometrial, breast, or colorectal cancer reflects independent oncogenic events rather than a shared molecular origin.