Loss of Dystrophin is common in Uterine Leiomyosarcoma: a potential biomarker for clinical application.

Uterine leiomyosarcoma (LMS) is a deadly disease with high rates of recurrence and a poor prognosis. Its tumorigenesis remains largely unknown, and no specific biomarkers can be used for the differential diagnosis of LMS from other mimics. Recent whole genome studies revealed a loss of dystrophin is common in LMS, especially uterine LMS. To investigate the expression pattern of dystrophin expression across different type of uterine smooth muscle tumors, immunohistochemistry was performed, including usual type leiomyoma, fumarate hydratase-deficient leiomyoma, leiomyoma with bizarre nuclei, conventional LMS and normal myometrium for this study. To further evaluate the genomic change in dystrophin gene region, whole genome sequencing in 10 LMS were analyzed. Dystrophin expression was detected in 94% (45/48) of myometrium, 97% (34/35) of usual type leiomyoma, 84% (26/31) of fumarate hydratase-deficient leiomyoma, 60% (12/20) of leiomyoma with bizarre nuclei, and 18% (6/34) of LMS. Loss of dystrophin expression was significantly different between benign and malignant tumors (LMS cases counted as malignant only) (p<0.01). Of note, copy number loss in the dystrophin genomic region was found in all ten cases of LMS. Additionally, patients with dystrophin positive LMS tend to have a better overall survival in comparison to patients with dystrophin negative LMS.