Endometriosis and cancer-driver mutations

A genomic analysis of endometriotic lesions shows that a disease associated with almost no risk of malignant transformation may harbor mutations associated with cancer. The findings, published in NEJM, provide a rationale for characterizing all endometriosis subtypes, say the authors.

For the study, researchers analyzed deeply infiltrating endometriotic lesions from 27 patients. They used exomewide sequencing in samples from two of the patients and cancer-driver-targeted sequencing in the other 3 patients. A droplet polymerase chain reaction (PCR) assay was used to assess for recurrent activating KRAS mutations in epithelial and stromal lesions from another 12 patients.

Somatic mutations were found in 19 of 24 lesions (79%) tested with exomewide sequencing. Five of those patients were found to have known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A. Likelihood of driver genes being affected at that rate in the absence of selection was estimated at P = 0.01. The PCR assay revealed KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient had 2 different KRAS mutations and another had identical KRAS mutations in 3 distinct lesions.

The authors noted that in total, 10 of 39 deep infiltrating lesions (26%) carried driver mutations and that all of the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions. Their findings, they said, “create new opportunities for a more detailed examination of all forms of endometriosis with the use of research approaches that are common in the study of cancer.