Molecular analysis suggests oligoclonality and metastasis of endometriosis lesions across anatomically defined subtypes

Abstract

To investigate the heterogeneity of somatic cancer-driver mutations within patients and across endometriosis types. A single-center cohort, retrospective study. Tertiary specialist-care center at a university hospital. Patients with surgically and histologically confirmed endometriosis of at least 2 anatomically distinct types (ovarian, deep infiltrating, and superficial). None. Specimens were analyzed for the presence or absence of somatic cancer-driver mutations using targeted panel sequencing with orthogonal validation using droplet digital polymerase chain reaction and mutation-surrogate immunohistochemistry. It was found that 13 of 27 patients had informative somatic driver mutations in endometriosis lesions; of these 13 patients, 9 had identical mutations across distinct lesions. Endometriomas showed a higher mutational complexity, with functionally redundant driver mutations in the same gene and within the same lesions. Our data are consistent with clonality across endometriosis lesions, regardless of subtype. Further, the finding of redundancy in mutations within the same gene and lesions is consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones traveling together. This suggests that the current anatomically defined classification of endometriosis does not fully recognize the etiology of the disease. A novel classification should consider genomic and other molecular features to promote personalized endometriosis diagnosis and care.