Epigenetic modification of the HAND2 gene plays a critical role in the development of endometrial cancer, suggests a new study published this week in PLOS Medicine. HAND2 is active in the healthy endometrium (the tissue lining the uterus) where it antagonizes the growth-inducing effects of estrogen. By contrast, in more than 90% of endometrial cancers, the gene has undergone hypermethylation, an epigenetic modification that doesn't change its DNA sequence but renders it inactive.
Martin Widschwendter from the University College London Women's Cancer Department and colleagues, the authors of the work, systematically compared methylation patterns in endometrial cancers and normal endometrium. Using a new bioinformatics tool, they identified HAND2 as a differential methylation hotspot in endometrial cancer. By comparing with other already known factors, HAND2 methylation is by far the most common molecular alteration in endometrial cancer.
The researchers found that HAND2 methylation is already increased in premalignant endometrial lesions (cancer-prone, abnormal-looking tissue) compared to normal endometrium, and that a high level of methylation predicted a poor response to progesterone treatment (which stops the growth of some pre-cancerous endometrial lesions).