Epigenetic causes of prostate cancer

September 5, 2012

(Medical Xpress)—In about half of all prostate tumours, there are two genetic areas that are fused with one another. When this is not the case, the exact way cancer cells originate in prostate tumours was not clear until now. Scientists at the Max Planck Institute for Molecular Genetics in Berlin, in cooperation with a team of international researchers, were able to show that the genesis of this fusion-negative prostate cancer has epigenetic causes: methyl groups are distributed differently over the DNA in the cancer cells than in healthy cells. Thanks to this knowledge, physicians may be able to achieve greater specificity in treating prostate tumours in future. In addition, the aberrant DNA methylations can be used as a potential biomarker for identifying prostate cancer.

About half of all cases of prostate cancer originate through fusion of two genetic areas. As a result, the ERG gene is activated in these fusion-positive cells and propagate, leading to tumourigenesis. Fusion-positive prostate cancer can be treated with PARP1 inhibitors that turn off the repair system of the .

However, it has not been clear how prostate tumours without a fused ERG gene acquire their tumourigenic potential. Now, a team of scientists headed by Michal-Ruth Schweiger from the Department of Vertebrate Genomics have investigated the global DNA methylation pattern – i.e. at which locations the DNA possesses methyl groups – in fusion-negative tumours. They have discovered that, compared to fusion-positive tumours, the fusion-negative tumours display more aberrant DNA methylations, which are most likely causative for the malignant transformation of prostate cells.

Moreover, the scientists found large amounts of the enzyme EZH2 in the cells of the tumours. This histone methyltransferase couples histone and DNA methylation and also transfers methyl groups to the DNA. Further functional analyses link EZH2 to the aberrant DNA methylations in negative tumours. As reason for the significantly increased amount of EZH2 the scientists found very low concentrations of miRNA-26a, a micro-RNA that targets EZH2 for degradation.

The researchers think that their findings will further enhance diagnosis and specific treatment options for prostate cancer patients. "Regions with different patterns can be used as biomarkers to diagnose specific subgroups of cancer", says Schweiger. "In addition, new medications for fusion-negative prostate cancer could operate with greater specificity and therefore be more effective." It is likely that other types of cancer are also based on these kinds of pronounced epigenetic modifications.

Explore further: Abnormal gene product associated with prostate cancer generated by unusual mechanism

More information: Börno ST, et al. Genome-wide DNA methylation events in TMPRSS2:ERG fusion negative prostate cancers implicate an EZH2 dependent mechanism with miRNA-26a hypermethylation. Cancer Discovery, Published Online First August 28, 2012; doi: 10.1158/2159-8290.CD-12-0041

Related Stories

Abnormal gene product associated with prostate cancer generated by unusual mechanism

June 19, 2012
Researchers have identified a potential new pathway in prostate cancer cells by which cancer-driving gene products can be generated, according to a study published in Cancer Discovery, a journal of the American Association ...

Half of prostate cancers could potentially benefit from new type of cancer drugs, study finds

May 18, 2011
About half of prostate cancers have a genetic anomaly that appears to make tumor cells responsive to a new class of cancer-fighting drugs, a new study from the University of Michigan Comprehensive Cancer Center finds.

Researchers discover biomarkers for prostate cancer detection, recurrence

May 14, 2012
Alterations to the "on-off" switches of genes occur early in the development of prostate cancer and could be used as biomarkers to detect the disease months or even years earlier than current approaches, a Mayo Clinic study ...

Investigational agent shows promise in reducing spread of prostate cancer

April 29, 2011
A drug developed to treat Ewing's Sarcoma, a rare childhood cancer, may also help prevent human prostate cancer from spreading, as seen in new lab studies say researchers at Georgetown Lombardi Comprehensive Cancer Center, ...

Recommended for you

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

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.