(Press-News.org) More than 500,000 people in the United States die each year of cancer-related causes. Now, emerging research has identified the mechanism behind one of the most common mutations that help cancer cells replicate limitlessly.
Approximately 85 percent of cancer cells obtain their limitless replicative potential through the reactivation of a specific protein called telomerase (TERT). Recent cancer research has shown that highly recurrent mutations in the promoter of the TERT gene are the most common genetic mutations in many cancers, including adult glioblastoma and hepatocellular carcinoma.
TERT stabilizes chromosomes by elongating the protective element at the end of each chromosome in a cell. Scientists have discovered that cells harboring these mutations aberrantly increase TERT expression, effectively making them immortal.
Now, a collaborative team of researchers at the University of Illinois at Urbana-Champaign and at the University of California, San Francisco, has uncovered the mechanisms by which these common mutations result in elevated TERT expression. The team's findings, published May 14 in Science, have exciting implications for new, more precise and personalized cancer treatments with fewer side effects compared with current treatments.
By integrating computational and experimental analyses, the researchers identified that the mechanism of increased TERT expression in tumor tissue relies on a specific transcription factor that selectively binds the mutated sequences. A transcription factor is a protein that binds specific DNA sequences and regulates how its target genes are expressed (in this case the gene that expresses TERT). Thus, the TERT mutations act as a new binding site for the transcription factor that controls TERT expression. The newly identified transcription factor does not recognize the normal TERT promoter sequence, and thus, does not regulate TERT in healthy tissue.
The researchers at Illinois include H. Tomas Rube, Alex Kreig, Sua Myong, and Jun S. Song. UCSF collaborators include Robert J. A. Bell, Andrew Mancini, Shaun F. Fouse, Raman P. Nagarajan, Serah Choi, Chibo Hong, Daniel He, Melike Pekmezci, John K. Wiencke, Margaret R. Wrensch, Susan M. Chang, Kyle M. Walsh, and Joseph F. Costello. The first author, Robert Bell, is a graduate student at UCSF co-mentored by Dr. Song and Dr. Costello.
The team's work further showed that the same transcription factor recognizes and binds the mutant TERT promoter in tumor cells from four different cancer types, underscoring that this is a common mechanism of TERT reactivation.
The identified transcription factor and its regulators have great potential for the development of new precision therapeutic interventions in cancers that harbor the TERT mutations. A treatment that would inhibit TERT in a targeted cancer-cell-specific manner would bypass the toxicities associated with current treatments that inadvertently also target TERT in normal healthy cells.
Based on these new findings, the team is now conducting a variety of experiments designed to test whether inhibiting the transcription factor activity would not only turn down TERT expression, but might also result in selective cancer cell death.
INFORMATION:
This project was enhanced by the complementary analysis conducted by three research groups located across the country. Joseph F. Costello's laboratory at UCSF is linked to the UCSF Medical Center and the Helen Diller Family Comprehensive Cancer Center, which allowed for access to human tumor samples that generated the cell cultures and produced relevant models. Jun Song's group at Illinois provided advanced computational analysis of the genomic data and predictions that narrowed in on possible mechanisms behind the previously identified mutation. Finally, through single-molecule analysis, Su-A Myong's lab at Illinois provided verification that the proposed mechanism operated in the suggested matter.
The article abstract, "The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer," is available online at https://www.sciencemag.org/content/early/2015/05/13/science.aab0015.abstract.
Adolescents who sleep less or stay up later are significantly more likely to have used alcohol and marijuana over the past month when compared to their peers who report better sleep patterns, according to a new RAND Corporation study.
Studying adolescents in Southern California, researchers found that the association between sleep and alcohol/marijuana use was consistent even after controlling for other known risk factors, such as depression.
The findings, published online by the journal Sleep Health, were generally consistent across racial and ethnic groups.
"Our ...
WASHINGTON, D.C., May 18, 2015 - Wind turbines causing cluckus interruptus in prairie chickens, tranquility at a conservation center, better blood pressure monitors with wearables, improved voice recognition software, language emergence with cochlear implants, and a vibrational analysis of graphite tennis rackets are just some of the highlights from the lay-language versions of papers to be presented at the 169th meeting of the Acoustical Society of America (ASA), held May 18-22 in Pittsburgh.
These summaries are posted online in the ASA's Pressroom; many contain sounds, ...
MISSOULA, MONTANA - University of Montana Assistant Professor John McCutcheon has once again discovered something new about the complex and intriguing inner workings of the cicada insect.
The Proceedings of the National Academy of Sciences recently published his findings online. In a paper titled "Genome expansion by lineage splitting and genome reduction in the cicada endosymbiont Hodgkinia," McCutcheon and his team found that the nutritional symbionts living inside long-living cicadas have become a lot more complicated. And it's not necessarily a good thing for the ...
A mass media campaign intended to help prevent suicides in California is reaching a majority of the state's adults and appears to be increasing their confidence about how to intervene with those at risk of suicide, according to new RAND Corporation research.
In addition, an assessment of a companion suicide prevention program finds that for each year the program is operated, the long-term impact could be the prevention of at least 140 deaths and 3,600 suicide attempts over the next three decades.
The analysis also estimates that for every $1 the state invests in the ...
WASHINGTON (May 18, 2015) -- Hospitals performing carotid artery stenting vary considerably in rates of in-hospital stroke or death--from 0 to 18 percent overall and from 1.2 to 4.7 percent when accounting for variation in health of patients at admission, according to a study published today in JACC: Cardiovascular Interventions.
Using data from the American College of Cardiology's CARE Registry, the largest national registry of carotid artery stent patients, researchers assessed 19,381 procedures from 188 hospitals that each performed more than five carotid artery stenting ...
(WASHINGTON, May, 18, 2015) - Cancer patients with brain metastases who develop blood clots may safely receive blood thinners without increased risk of dangerous bleeding, according to a study, published online today in Blood, the Journal of the American Society of Hematology
Cancer increases a patient's risk of developing blood clots. When a patient with cancer develops a clot, treatment with a blood thinning medication called an anticoagulant is often added to their treatment regimen in order to prevent the potentially fatal complication of blood clots traveling to ...
In recent years, the popularity of "electronic dance music" (EDM) and dance festivals has increased substantially throughout the US and worldwide.
Even though data from national samples suggests drug use among adolescents in the general US population has been declining, targeted samples have shown nightclub attendees tend to report high rates of drug use, above that of the general population. In spite of increasing deaths among dance festival attendees in recent years, no nationally representative studies have examined potential associations between nightlife attendance ...
MAYWOOD, IL - As many as 12 percent of patients undergoing major, non-cardiac surgery experience an irregular heartbeat called atrial fibrillation.
Post-operative atrial fibrillation (POAF) often is dismissed as a transient phenomenon. But a Loyola University Medical Center study has found that POAF can significantly increase the risk of heart attack or stroke during the first 12 months after surgery.
Among bladder cancer patients who underwent a cystectomy (bladder removal) and developed POAF, 24.8 percent experienced a heart attack or stroke during the first 12 months ...
ATS 2015, DENVER ? Severe obstructive sleep apnea (OSA) and excessive daytime sleepiness are associated with an increased risk of depression in men, according to a new community-based study of Australian men, which was presented at the 2015 American Thoracic Society International Conference.
"An association between sleep apnea and depression has been noted in some earlier studies," said lead author Carol Lang, PhD, from the University of Adelaide, Australia. "Our study, in a large community-based sample of men, confirms a strong relationship even after adjustment for ...
New York, NY, May 18, 2015 -- The National Cancer Institute (NCI) recently announced that it had removed all prostate specific antigen (PSA) data from the SEER (Surveillance, Epidemiology and End Results) and SEER-Medicare programs. The PSA data were removed after quality control checks revealed that a substantial number of PSA values included in the programs were incorrect. An editorial published in The Journal of Urology® explores the ramifications of the removal of these data for researchers, clinicians, and administrators within the health care community, as well ...
