Early epigenetic changes in fallopian tubes suggest new strategies to prevent ovarian cancer
Key Takeaways
An early cellular change occurs in the fallopian tubes of women with the BRCA mutation, but it doesn’t occur in women without the mutation—a finding that may help explain why women with the mutation are at a much greater risk of ovarian cancer, according to a study published online May 24, 2016 in the journal Nature Communications.
The finding might also open the door for new strategies to prevent ovarian cancer and reduce the need for invasive surgery, the researchers said.
For this investigation, the researchers sought to understand the early molecular changes that occur in the development of ovarian cancer. They suspected that epigenetic reprogramming is a crucial step in cancer development; however, this cellular change-up is difficult to observe in humans. They decided to compare both ends of the fallopian tube because they knew that ovarian cancers originate only from the distal (or fimbrial) end of the fallopian tube (close to the ovary), and not from the proximal end (close to the uterus).
To that end, they examined post-surgical reproductive tubal tissue from 56 women with the BRCA1 or BRCA2 gene mutation and a control group of 59 women without it. The researchers performed epigenome-wide analyses of cells from the fimbrial end of the fallopian tube and compared those to the cells from the uterine end in each woman.
The researchers found that approximately 60% of women with the BRCA1/2 mutation had significant epigenetic reprogramming in the fimbrial tubal cells. (Incidentally, 60% is also the proportion of women with a BRCA1 mutation who are expected to develop ovarian cancer.) These subcellular changes were similar to those seen in cells from ovarian cancer specimens. Women without BRCA mutations had no such changes.
In addition, the researchers identified that aberrantly high expression of an enzyme (activation-induced cytosine deaminase, AID) drives this epigenetic reprogramming, and is integral to the early pre-malignant development of ovarian cancer.
“These new findings take us a step closer to understanding how ovarian cancers develop in BRCA1/2 gene mutation carriers, opening up new opportunities for ovarian cancer prevention. This is vital, as at present the most effective method of prevention is drastic risk-reducing surgery which deprives women of their hormones and their ability to give birth prior to menopause,” said lead researcher Martin Widschwendter, MD, Professor in Women’s Cancer at University College London, in London, UK.
“The next steps will be to investigate the merit of drugs that affect epigenetic reprogramming and to look for biomarkers which allow safe monitoring of the effect of such drugs,” added Dr. Widschwendter.