Navigation Links
Immortality gene mutation identifies brain tumors and other cancers

DURHAM, NC Newly identified mutations in a gene that makes cells immortal appear to play a pivotal role in three of the most common types of brain tumors, as well as cancers of the liver, tongue and urinary tract, according to research led by Duke Cancer Institute.

The finding, published Monday, March 18, 2013, in the journal Proceedings of the National Academy of Sciences, provides a long-sought answer to how some malignant cells are able to proliferate, while normal cells peter out and die.

This key to immortality involves telomeres, the end tabs that protect chromosomes from sticking together or fraying. As normal cells divide, the telomeres gradually grow shorter until they become so short the cell stops dividing and it expires. An enzyme called telomerase serves as a sort of growth factor, temporarily maintaining the length of the telomeres and enabling the cell to continue proliferating.

Scientists have recently learned that mutations of the so-called TERT promoter gene, which controls the instructions for making the telomerase enzyme, is involved in some cancer tumors. It appears that a mutation of the TERT promoter gene essentially creates a constant growth spurt so that the telomeres never shorten, and the cells can divide forever. Earlier this year, the process was described as a leading contributor to melanomas and a small number of other tumors.

The current research expands those findings by analyzing more than 1,200 tumors across 60 different types of cancer. Led by Hai Yan, M.D., PhD, a professor of pathology and investigator with Duke's Preston Robert Tisch Brain Tumor Center, the research team includes collaborators at Johns Hopkins and multiple other institutions.

The researchers found almost no TERT promoter mutations in many major cancer types, including breast and prostate malignancies, suggesting that some yet-unknown factor is causing the telomeres to elongate and promote cell immortality in those diseases.

But the Duke-led research team also identified nine tumor types highly associated with TERT promoter mutations. These cancers generally share a common feature: they arise in tissues with relatively low rates of cell renewal, suggesting they require the mutation to trigger the abnormal telomerase production.

These cancer types include melanomas, liposarcomas, hepatocellular carcinomas, transitional cell carcinomas of the urinary tract, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas, including 83 percent of primary glioblastomas, the most common brain tumor in adults with a median survival of only 15 months.

"The results in brain tumors were quite striking," said Patrick J. Killela, co-lead author of the study and a Duke graduate student. "For primary glioblastoma, this is the most frequent genetic mutation yet identified in this tumor."

Four years ago, Yan's laboratory at Duke identified critical gene mutations associated with glioblastoma. But those mutations in the IDH1 and IDH2 genes -- were found only in rare glioblastomas that arose from other, lower-grade tumors known as astrocytomas and oligodendrogliomas. The main cancer-causing mutation for the other primary glioblastomas remained elusive.

"Now we see this," said Zachary J. Reitman, Ph.D., an associate in research at Duke and co-lead author of the study. "This is a major discovery in brain tumors, because this single mutation can now distinguish one tumor from another and these are tumors that are difficult to classify with a typical pathology test. For primary glioblastoma, the TERT mutation is remarkably common, while for astrocytomas, it is rare. Using both IDH1 and TERT, we can greatly improve diagnosis and prognosis."

Yan said the TERT mutations also provide a biomarker that may be useful for early detection of urinary tract and liver tumors. The finding provides new targets for drug development.

"Cancer is very smart to have figured out a way to use a mechanism to live longer," Yan said. "Now that we know how it operates in these tumor types, we might be able to beat it at its own game."

Contact: Sarah Avery
Duke University Medical Center

Related medicine news :

1. Pursuing literary immortality illuminates how the mind works, finds CWRU researcher
2. KRAS gene mutation and amplification status affects sensitivity to antifolate therapy
3. Researchers Find Gene Mutations That May Be a Key to Autism
4. Mayo Clinic breast cancer study finds new type of mutation
5. Scientists make breakthrough in bile duct cancer with discovery of new gene mutations
6. Cancer may require simpler genetic mutations than previously thought
7. Mutations impair childhood growth and development by disrupting organization of chromosome pairs
8. Study sheds new light on role of genetic mutations in colon cancer development
9. Mutations in JAK3 gene identified in subtype of lymphoma provide potential drug target
10. Study finds new gene mutations that lead to enlarged brain size, cancer, autism, epilepsy
11. Gene Mutation Linked to Facial, Skull Abnormalities
Post Your Comments:
(Date:11/25/2015)... Jacksonville, FL (PRWEB) , ... November 25, 2015 ... ... treatment center, is encouraging people across the country to celebrate their sobriety and ... invites people to post “before and after” photos this Thanksgiving with the hashtag ...
(Date:11/25/2015)... (PRWEB) , ... November 25, 2015 , ... On November ... training center for the Narconon network, announced the release of a new cutting edge ... the Narconon organization has been working with drug- and alcohol-addicted individuals with the purpose ...
(Date:11/25/2015)... ... , ... The McHenry County law firm of Botto Gilbert Lancaster, PC ... J. Botto and Alex C. Wimmer. Attorneys Botto and Wimmer represented the claimant David ... 130884WC. , According to court documents, Adcock testified that on May 10, 2010 he ...
(Date:11/25/2015)... ... November 25, 2015 , ... Smiles by Stevens is pleased ... moderate facial wrinkling. While many patients are aware of the benefits of Botox® in ... delivers to those suffering with discomfort, soreness, and pain as a result of Jaw ...
(Date:11/25/2015)... ALTO, Calif. (PRWEB) , ... November 25, 2015 , ... ... Smart and Beddit Classic sleep tracking systems. The new app features a more intuitive ... see and understand how well you slept. The SleepScore is created by a proprietary ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... N.Y. , Nov. 25, 2015  Henry Schein, ... and services to office-based dental, medical and animal health ... (GNYDM) Meeting the Henry Schein ConnectDental® Pavilion , ... broadest array of open solutions designed to help any ... Click here for a schedule of experts ...
(Date:11/25/2015)... SAN DIEGO , Nov. 25, 2015  Trovagene, ... molecular diagnostics, today announced that Chief Executive Officer Antonius ... at the 27 th Annual Piper Jaffray Healthcare ... Conference at the New York Palace Hotel in ... 2015 at 1:30 p.m. EST. Mr. Schuh will be ...
(Date:11/25/2015)... 2015 Endo International plc (NASDAQ: ENDP ) ... President and CEO, will discuss corporate updates at the 27 ... New York on Wednesday, December 2, 2015 at ... Investor Relations, and then the link to the event. Participants ... time to visit the site and download any streaming media ...
Breaking Medicine Technology: