Cancer-associated mutations in endometriosis without cancer

Scientists from the BC Cancer Agency, the BC Women’s Hospital, Vancouver Coastal Health, the University of British Columbia, and John Hopkins have found cancer-causing gene mutations in pelvic lesions of women with endometriosis – which is a non-cancerous condition.

The research was published by the New England Journal of Medicine [1], and may raise the possibility of using some experimental cancer drugs for chronic endometriosis, according to lead author Michael Anglesio:

Finding these mutations in non-cancer conditions is largely uncharted territory. It’s not just inflammation around endometrial tissue in the wrong place, it’s that there are genetic changes hardwired into the biology of endometriosis.

Drs Paul Yong and Michael Anglesio, BC Women’s Hospital

A very low percentage of cases of endometriosis are linked to a type of ovarian cancer, but this study showed that most of the tissue samples had mutations linked to cancer.

The researchers limited their study to investigate only deep endometriosis, which is associated with virtually no risk of malignant transformation. They found that these deep lesions harbour somatic cancer driver mutations. Ten of 39 deep lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.

Thus the study adds to the intrigue about endometriosis, which may share the same features and molecular makeup as cancerous growths that lead to tumours in other areas of the body – without it being cancerous.

An editorial in the same issue of the NEJM says it may be that although there are DNA errors in endometriosis, they may not be numerous enough to cause cancer.

According to co-author, Dr Paul Yong, this study has implications beyond gynaecologic oncology:

It is possible that mutations usually associated with cancer may not always be so menacing as to cause cancer. But scientists needs to learn more, through a bigger, longer study, about what puts the brakes on the mutations, especially if there are certain “micro-environments” that hinder the transformation of growths from being merely abnormal to becoming malignant.

Dr Anglesio concluded:

These mutations are a first step in understanding the breadth of symptoms and outcomes that affect every woman with endometriosis differently. Finally, we have a roadmap towards finding better treatments.

Dr Yong will present the findings at the 13th World Congress on Endometriosis, which takes place next week held in Vancouver.