Navigation Links
Immortality gene mutation identifies brain tumors and other cancers
Date:3/18/2013

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
sarah.avery@duke.edu
919-660-1306
Duke University Medical Center
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... , ... Talented host, actor Rob Lowe, is introducing a ... episode of "Success Files," which is an award-winning educational program broadcasted on PBS ... in-depth with passion and integrity. , Sciatica occurs when the sciatic nerve in ...
(Date:10/12/2017)... ... October 12, 2017 , ... First Healthcare Compliance (FHC), an ... showcase a range of technology and learning solutions at the 68th Annual American ... to be held October 14–18, 2017 at the Mandalay Bay Resort in Las ...
(Date:10/12/2017)... ... 12, 2017 , ... IsoComforter, Inc. ( https://isocomforter.com ), one of ... innovative new design of the shoulder pad. The shoulder pad provides optimal support ... your pain while using cold therapy. By utilizing ice and water that is circulated ...
(Date:10/12/2017)... ... October 12, 2017 , ... Dr. Parsa Mohebi, the ... medical article to the newly revamped Cosmetic Town journal section, featuring ... transplant procedure known as Follicular Unit Extraction (FUE). , Dr. Mohebi ...
(Date:10/12/2017)... ... October 12, 2017 , ... Women-owned and Grand ... Best and Brightest in Wellness® by Best and Brightest. OnSite Wellness will be ... Oct. 20 from 7:30 a.m. to 2 p.m. at the Henry Autograph Collection ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... DIEGO , Oct. 12, 2017 AVACEN ... recognized the company with their  2017 New Product Innovation Award ... based on extensive primary and secondary medical device market research ... Medical, through its first-to-market OTC, drug-free pain relief product, the ... unique approach to treating fibromyalgia widespread pain. ...
(Date:10/12/2017)... , Oct. 12, 2017 West Pharmaceutical ... innovative solutions for injectable drug administration, today announced that ... market opens on Thursday, October 26, 2017, and will ... and business expectations at 9:00 a.m. Eastern Time. To ... 253-336-8738 (International). The conference ID is 94093362. ...
(Date:10/11/2017)... IRVING, Texas , Oct. 11, 2017  Caris ... science focused on fulfilling the promise of precision medicine, ... Institute has joined Caris, Precision Oncology Alliance™ (POA) as ... leading cancer centers, the St. Jude Crosson Cancer Institute ... to advance the use of tumor profiling, making cancer ...
Breaking Medicine Technology: