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

Abstract

Endometriosis has yielded controversy on whether it constitutes a single disease or distinct types. Current classification systems poorly correlate with the severity of symptoms and do not provide prognostic tools that can guide management or predict recurrence or success of treatment. Our previous work has uncovered recurrent cancer-driver alterations in endometriosis. Here we examined anatomically separate types of endometriosis (ovarian endometriomas, deep infiltrating, and superficial endometriosis) in 27 individual patients for evidence of a common origin. Specimens were analyzed using high-sensitivity targeted sequencing with orthogonal validation from droplet digital PCR and mutation-surrogate immunohistochemistry. Results show clonality between lesions is common (observed in 9/27 cases) and that endometriomas have potential for higher mutational load, often resulting in multiple subclonal lineages. Our data further confirms that endometriosis is generally an oligoclonal disease with dissemination likely to consist of multiple epithelial clones travelling together.