Multigene Analysis in Women with Precancerous Conditions of The Endometrium and in Patients with Endometrial Carcinoma

Abstract This study investigated germline and somatic mutations in endometrial precancerous conditions and endometrial carcinoma to elucidate the molecular landscape of endometrial cancer development. Germline pathogenic variants were identified in 30.14% of endometrial precancerous cohort patients (n = 205). The most frequently altered genes in the endometrial precancerous cohort were CHEK2 , SOS1 , NBN , and SLX4 . In the endometrial carcinoma cohort (n = 39), 20.51% of patients had germline PVs. Somatic mutation analysis of endometrial tumor tissues revealed frequent variants in PTEN , PIK3CA , ARID1A , and TP53 . Notably, the mean age of patients with germline pathogenic variants did not significantly differ from those without, in either cohort. We observed a higher prevalence of hereditary breast and ovarian cancer-associated PVs compared to Lynch syndrome-associated pathogenic variants in the endometrial precancerous cohort. Our findings underscore the importance of comprehensive genetic testing in individuals with endometrial precancerous lesions and contribute to a deeper understanding of the genetic factors influencing endometrial carcinoma development.