Novel CTCF mutations in Chinese patients with ovarian endometriosis

Endometriosis is a common gynecological disease characterized by the outgrowth of the endometrium, however, the detailed molecular etiology remains largely uncharacterized. Recent studies have implicated that endometriosis is potentially a precancerous lesion, and that CCCTC‑binding factor (CTCF) mutations may be involved in the pathogenesis of this disorder. However, the detailed CTCF mutation spectrum in Chinese patients with ovarian endometriosis remains largely unknown. In the present study, a cohort of 92 patients with ovarian endometriosis were analyzed for the presence of CTCF mutations by sequencing the entire coding regions. In addition, 67 healthy eutopic endometrial tissues and 46 healthy ovarian tissues from control samples (without endometriosis) were also analyzed. In total, two CTCF missense mutations, p.K206E (c.616A>G) and p.H373L (c.1118A>T), were identified in 2/92 (2.2%) endometriotic lesions. The patient with the p.K206E mutation was 26 years old and diagnosed with primary infertility, whereas the patient with the p.H373L mutation was 37 years old and concurrently diagnosed with uterine leiomyoma. The p.H373L mutation was previously identified in endometrial cancer samples with low frequency, while the p.K206E mutation was novel. In addition, no CTCF mutations were detected in the 67 healthy eutopic endometrial and 46 healthy ovarian tissue samples. In silico prediction and evolutionary conservation analysis suggested that these CTCF mutations may be pathogenic. In summary, the present study identified 2 potential pathogenic CTCF mutations in endometriotic lesions from 2/92 patients with ovarian endometriosis. These results, together with a prior exome‑sequencing based study, suggest that CTCF mutations may be involved in the development of ovarian endometriosis.