Nearly All Endometrial Cancers Have One Thing in Common, Study Finds

More than 90% of endometrial cancers show that the HAND2 gene has been turned off, leading researchers to believe that the epigenetic modification of the gene plays a critical role in the development of endometrial cancer, according to a recent study.

HAND2 is a progesterone-regulated stem cell polycomb group target gene that encodes a transcription factor that is expressed in the endometrial stroma, where most endometrial cancers develop. (Polycomb genes control the expression of their target genes by modifying their DNA or associated proteins, explained the study authors.)

The authors used a new bioinformatics tool to compare methylation patterns in endometrial cancers and normal endometrium. In the study, they collected data on genome-wide DNA methylation at cytosine- and guanine-rich sites in endometrial cancers and normal endometrium. The data was then integrated with the physical interactions between proteins and all the genes expressed in a cell using an algorithm.

Through the process, the researchers identified HAND2 as being the center hotspot in endometrial cancer because it showed the most highly ranked differential methylation. By comparing the new information with other known factors, they concluded HAND2 methylation is by far the most common molecular alteration in endometrial cancer.

"Our work provides clear evidence that it is not only genetic alterations which trigger and lead to cancer but that epigenetic alteration can also be the initiating step," said the study’s lead author Martin Widschwendter from the University College London Women’s Cancer Department.

The researchers said that HAND2 methylation could also be a biomarker for early cancer detection, because the methylation of the gene is increased even in premalignant endometrial lesions.

In addition, the researchers suggested the gene’s methylation could also be used as a predictor of treatment response, because analysis for HAND2 methylation in endometrial secretions collected from women with postmenopausal bleeding accurately diagnosed early stage cancer. The study showed that the presence of a high level of methylation predicted a poor response to progesterone treatment to stop the growth of pre-cancerous cells in those cancer-prone, abnormal tissues.

Still, the authors concluded that even though their worked found “HAND2 methylation is a common and crucial molecular alteration in endometrial cancer,” further study is needed to validate the clinical application and utility.

Pertinent Points:
- Researchers have identified the HAND2 gene methylation as being a crucial molecular alteration in the development of endometrial cancer.
- The researchers believe that their study shows evidence that epigenetic alteration can be an initiating step in the development of endometrial cancer and that further study is needed to vet out the clinical applications of their discovery.

References:

Jones A, Teschendorff AE, Hayward JD, et al. Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development. PLOS Med. November 12, 2013. DOI: 10.1371/journal/pmed.1001551.