Epigenetic silencing of the HAND2 tumor suppressor promotes endometrial cancer

November 12, 2013, Public Library of Science

A study published this week in PLOS Medicine suggests that epigenetic modification of the HAND2 gene plays a critical role in the development of endometrial cancer. 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 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 ) 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).

Moreover, analysis of HAND2 methylation in endometrial secretions collected from women with postmenopausal bleeding (which can be a symptom of endometrial cancer) accurately identified individuals with early stage cancer. Finally, mice in which the Hand2 gene was specifically deleted in the endometrium developed precancerous endometrial lesions with age. Widschwendter, who led the study, said: "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." Endometrial cancer is the most common gynecological cancer, and its incidence is continuing to rise in an older and more obese population. The authors suggest that HAND2 methylation "could be applied to triage women who present with postmenopausal bleeding (currently ~90% of women who present with this symptom and are cancer-free must undergo endometrial biopsy for a definitive diagnosis) and could be further employed as a test to early detect or even predict the risk for endometrial cancer and response to preventative treatment".

Explore further: Common birth control device may be cost-effective treatment for early endometrial cancer

More information: Jones A, Teschendorff AE, Li Q, Hayward JD, Kannan A, et al. (2013) Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development. PLoS Med 10(11): e1001551. DOI: 10.1371/journal.pmed.1001551

Related Stories

Common birth control device may be cost-effective treatment for early endometrial cancer

October 16, 2012
A common birth control device is effective in treating early-stage endometrial cancer in morbidly obese and high-risk surgery patients, said Georgia Health Sciences University Cancer Center researchers, and could lead to ...

Nearly 60 percent of uterine cancer cases preventable, report says

September 11, 2013
(HealthDay)—Regular physical activity and maintaining a healthy weight can prevent three of every five new cases of endometrial cancer in the United States, according to a new review of scientific evidence.

Controlling the hormonal environment in endometrial cancer sensitizes tumors to PARP inhibitors

November 12, 2013
Modulating the hormonal environment in which endometrial cancers grow could make tumors significantly more sensitive to a new class of drugs known as PARP inhibitors, UCLA researchers have shown for the first time.

Hormonal treatment for endometrial cancer does not directly target the malignant cells

June 11, 2013
Progesterone, a female hormone that can be used as a therapy for endometrial cancer, eliminates tumor cells indirectly by binding to its receptor in stromal or connective tissue cells residing in the tumor microenvironment, ...

Significant weight gain in adulthood increased risk for endometrial cancer

October 24, 2011
Postmenopausal women who gained weight during adulthood had an increased risk for endometrial cancer compared with women who maintained a stable weight, according to data from the American Cancer Society's Cancer Prevention ...

Recommended for you

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

Combining three treatment strategies may significantly improve melanoma treatment

December 12, 2018
A study by a team led by a Massachusetts General Hospital (MGH) investigator finds evidence that combining three advanced treatment strategies for malignant melanoma—molecular targeted therapy, immune checkpoint blockade ...

Lethal combination: Drug cocktail turns off the juice to cancer cells

December 12, 2018
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth—this was discovered by researchers from the University of Basel's Biozentrum two years ago. In a follow-up study, ...

Researchers use computer model to predict prostate cancer progression

December 12, 2018
An international team of cancer researchers from Denmark and Germany have used cancer patient data to develop a computer model that can predict the progression of prostate cancer. The model is currently being implemented ...

An integrated approach to finding new treatments for breast cancer

December 12, 2018
Unraveling the complexity of cancer biology can lead to the identification new molecules involved in breast cancer and prompt new avenues for drug development. And proteogenomics, an integrated, multipronged approach, seems ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.