Metastasis in endometriosis: targeted sequencing suggests non-malignancy associated endometriosis is capable of wide dissemination

Objective Multiple forms of endometriosis have been shown to harbour somatic cancer-driver alterations. Previous studies have focused on the inter-patient heterogeneity of genetic alterations in endometriosis, analyzing lesions collected from the same anatomical types of endometriosis across different patients. The aim of our study was to explore intra-patient heterogeneity and potential clonal relationships of multiple anatomically separated lesions of distinct types of endometriosis within a given patient.

Materials and methods We examined endometriosis lesions of patients with multiple anatomically separated lesions, and each having at least two distinct types of endometriosis. Samples were assayed with a high sensitivity targeted sequencing panel and findings validated with droplet digital PCR and mutation-surrogate immunohistochemistry.

Results 73 endometriosis lesions from 27 patients were analyzed. Results found 13/27 patients had informative somatic driver mutation in endometriosis, of these 9/13 had identical mutations across distinct lesions. Endometriomas showed a higher mutational complexity, with functionally redundant driver mutations within the same gene.

Conclusions Our data are consistent with clonality across endometriosis lesions regardless of subtype. Further the finding of redundancy in mutations with the same gene and lesions is also consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones travelling together. This suggests 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.

These findings could further contribute to the development of a more personalized endometriosis diagnosis and care.

Publikationsverlauf

Artikel online veröffentlicht:
11. Oktober 2022