Navigation Links
Genetic changes outside nuclear DNA suspected to trigger more than half of all cancers
Date:3/24/2009

A buildup of chemical bonds on certain cancer-promoting genes, a process known as hypermethylation, is widely known to render cells cancerous by disrupting biological brakes on runaway growth. Now, Johns Hopkins scientists say the reverse process demethylation which wipes off those chemical bonds may also trigger more than half of all cancers.

One potential consequence of the new research is that demethylating drugs now used to treat some cancers may actually cause new cancers as a side effect.

"It's much too early to say for certain, but some patients could be at risk for additional primary tumors, and we may find that they need a molecular profile of their cancer before starting demethylating therapy," says Joseph Califano, M.D., professor of otolaryngologyhead and neck surgery and oncology at Johns Hopkins.

The findings, based on studies of normal and cancer cells from human mouth, nose and throat tissue, provide more evidence that important regulators of gene activity occur outside as well as inside DNA in a cell's nucleus.

"While cancer-causing and other mutations alter vital protein-making pathways by rewriting the gene's DNA code, epigenetic changes affect genes without changing the code itself. The new studies tell us that such changes occur not only when methyl groups bond to a gene's on-off switch, but also when they come unglued," says Califano.

Califano says sporadic reports of demethylation as a tool in activating cancer-promoting genes led his team to develop a systematic way to discover these epigenetic changes and show how the process is linked to cancer.

To gather their evidence, Califano and his group treated two cell lines from normal oral tissue with the demethylating drug 5-azacytidine and collected a list of genes that were activated as a result. They used special silicon chips carrying pieces of genetic material that allow thousands of genes to be analyzed at one time to locate genes activated by demethylation.

The list was cross-referenced with genes "turned on" in 49 head and neck cancer samples and 19 normal tissue samples. In all, Califano and his team found 106 genes specific to head and neck cancer that were activated by the demethylation process. "Some of the genes regulate growth, others metabolize sugars and some have already been linked to cancer development," says Califano, who is director of head and neck cancer research at the Milton J. Dance Jr. Head & Neck Center at Greater Baltimore Medical Center. A report on this work appears on March 23 in PLoS One.

Further analysis by the Johns Hopkins team revealed a single connection among 106 genes: methylation within them is regulated by another gene called BORIS. BORIS acts as a "master regulator," recruiting other proteins to demethylate a coordinated set of genes and signaling the development of cancer. According to the scientists, nearly 60 percent of a wide range of cancers, including head and neck and lung cancer, have high levels of BORIS expression.

He envisions that agents like 5-azacytidine may need to be combined with a "BORIS blocker," a drug that has yet to be developed to protect patients who need demethylating therapies.


'/>"/>

Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. Many Parents Share Genetic Test Findings With Kids
2. Genetic predisposition increases childhood asthma risk
3. New Alzheimers findings: High stress and genetic risk factor lead to increased memory decline
4. Test Spots Genetic Damage Done by Smoking
5. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
6. Scientists highlight benefits of genetic research in sport, but warn of ethical concerns
7. Genetics Hold Promise, Challenges for Cancer Care
8. Researchers genetically engineer micro-organisms into tiny factories
9. Study Questions Genetic Screening for Treatable Diseases
10. Researchers provide genetic associations from a genome-wide scan for cardiovascular disease traits
11. Genetic variation affects smoking cessation treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/25/2017)... , ... April 25, 2017 , ... Lake Park Dental ... by using Invisalign® in Lutz, FL. With the help of this highly-effective, ... aesthetics with fewer potential complications, more discretion and less pain. , Drs. Sarah ...
(Date:4/25/2017)... (PRWEB) , ... April 25, 2017 , ... Buyers and ... recreational users to dispensaries and head shops –can’t help but be heartened by the ... the tell-tale cannabis odor aptly described as “skunk smell.” At last they can ...
(Date:4/25/2017)... ... April 25, 2017 , ... ... healthcare products, is introducing Flexadin UCII, part of the EQUISTRO line, at this ... joint health in horses at the immunologic level. , The scientifically-developed Flexadin UCII ...
(Date:4/24/2017)... ... April 24, 2017 , ... The Santana Telehealth Project was honored with the ... the American Telemedicine Association’s annual conference, on April 23 in Orlando, FL. , “I ... improve the lives of the poor and underserved in other parts of the world,” ...
(Date:4/24/2017)... ... ... Bright Pink , a national non-profit organization focusing on the prevention and early detection ... Pink is proud to announce Katie Thiede as their new Chief Executive Officer. In January, ... Chairman of the Board and launched a national search to find a visionary new leader ...
Breaking Medicine News(10 mins):
(Date:4/20/2017)... 2017 Eyevensys, a private biotechnology ... gene expression technology that enables the safe, local, sustained ... a wide range of ophthalmic diseases, announces it has ... Regulatory Agency (MHRA) to advance its technology into clinical ... The ...
(Date:4/20/2017)... , April 20, 2017 Research and ... Pharmaceutical Contract Manufacturing Services Market Analysis By Service (Manufacturing, Research), ... Forecasts, 2014 - 2025" report to their offering. ... The Latin American pharmaceutical ... billion by 2025 Low drug registration cost in ...
(Date:4/19/2017)... Cardiology devices segment is anticipated to reach the highest market ... segment is likely to create absolute $ opportunity of a ... By the end of 2027, Cardiology Devices segment is projected ... expanding at a CAGR of 18.4% over the forecast period. ... reprocessed medical devices market in terms of revenue ...
Breaking Medicine Technology: