Navigation Links
Researchers discover new mutations driving malignant melanoma
Date:1/24/2013

BOSTONTwo new mutations that collectively occur in 71 percent of malignant melanoma tumors have been discovered in what scientists call the "dark matter" of the cancer genome, where cancer-related mutations haven't been previously found.

Reporting their findings in the Jan. 24 issue of Science Express, the researchers from Dana-Farber Cancer Institute and the Broad Institute said the highly "recurrent" mutations occurring in the tumors of many people may be the most common mutations in melanoma cells found to date.

The researchers said these cancer-associated mutations are the first to be discovered in the vast regions of DNA in cancer cells that do not contain genetic instructions for making proteins. The mutations are located in non-protein-coding DNA that regulates the activity of genes.

This non-coding DNA, much of which was previously dismissed as "junk," accounts for 99 percent of a cell's genome. A large number of oncogenic mutations in cancer have been identified in the past several decades, but all have been found within the actual genetic blueprints for proteins.

"This new finding represents an initial foray into the 'dark matter' of the cancer genome," said Levi Garraway, MD, PhD, of Dana-Farber and the Broad and the article's senior author.

"In addition, this represents the discovery of two of the most prevalent melanoma gene mutations. Considered as a whole, these two TERT promoter mutations are even more common than BRAF mutations in melanoma. Altogether, this discovery could cause us to think more creatively about the possible benefits of targeting TERT in cancer treatment or prevention."

The mutations affect a promoter region a stretch of DNA code that regulates the expression of a gene adjacent to the TERT gene. TERT contains the recipe for making telomerase reverse transcriptase, an enzyme that can make cells virtually immortal, and is often found overexpressed in cancer cells. A promoter region of DNA controls the rate of a gene's transcription the copying of its DNA recipe into a message used by the cell to manufacture a protein.

"We think these mutations in the promoter region are potentially one way the TERT gene can be activated," said Franklin Huang, MD, PhD, co-first author of the report along with Harvard MD-PhD student Eran Hodis, of Dana-Farber and the Broad Institute.

To investigate the mutation's effect, the researchers hooked the mutant TERT promoter to a gene that makes luciferase a light-emitting protein. They observed that the mutant promoter increased the production of luciferase in laboratory cell lines. In the same way, the scientists presume, the mutant promoter in human pigmented skin cells can send the TERT gene into overdrive, potentially contributing to the development of melanoma.

The mutations were discovered when the scientists sifted through data from whole-genome sequencing of malignant melanoma tumors. Unlike "whole-exome" searches that examine only the protein-coding DNA of a cell's genome, whole-genome searches scan all of the DNA, including the non-coding regions.

In analyzing whole-genome data, the investigators discovered the two somatic, or not-inherited, mutations in 17 of 19 (89 percent) of the tumors. Next, they sequenced a larger number of melanoma tumors and found that the two mutations were present in 71 percent of tumors in total.

The researchers said the same mutations are present in cell lines from some other malignancies, and that preliminary evidence showed they might be unusually common in bladder and liver cancers. They also noted that the discovery of these important mutations in DNA previously not linked to cancer-causing alterations highlights the value of whole-genome searches of tumor DNA.


'/>"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

Related medicine news :

1. CDC Researchers Spot Increase in New Stomach Bug Strain
2. Researchers prevent cancer spread by blocking tissue scarring
3. Researchers uncover genes role in rheumatoid arthritis, findings pave way for new treatments
4. New drug improves survival in multiple myeloma relapse, Moffitt Cancer Center researchers say
5. Researchers discover promising prognostic marker for aggressive breast cancer
6. Researchers design a new imaging technique for identifying the age and sex of a corpse
7. Researchers map emotional intelligence in the brain
8. Researchers find that simple blood test can help identify trauma patients at greatest risk of death
9. Mayo Clinic researchers identify enzyme involved in deadly brain tumors
10. UNC researchers use luminescent mice to track cancer and aging in real-time
11. Gothenburg researchers make world top 10
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers discover new mutations driving malignant melanoma
(Date:12/7/2016)... Honolulu, HI (PRWEB) , ... December 07, 2016 ... ... Dermatology is proud to announce that its fully redesigned website, which launched October ... well as a sleek responsive design and easy-to-navigate layout. Visitors and patients can ...
(Date:12/7/2016)... ... December 07, 2016 , ... The medical profession is well aware that ... One major study analyzing heart attacks among 138,602 people recorded a 35% higher number ... We would all agree of course–no time of year is a good time for ...
(Date:12/7/2016)... ... ... “The Road To Restoration”: an informative and enlightening book for those who believe ... hands. “The Road To Restoration” is the creation of published author, Thomas Fitzhugh Sheets, ... that you could reach out for, and grab, on the old carousels. If ...
(Date:12/7/2016)... Soquel, Caloifornia (PRWEB) , ... December 07, 2016 ... ... to present the fifth annual Business Architecture Innovation Summit in Reston, VA on ... the world who will share a range of experiences from a cross-section of ...
(Date:12/6/2016)... ... 2016 , ... The International Vaccine Institute (IVI) and GeneOne ... Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The collaboration will accelerate MERS-CoV vaccine development ... in the event of a future outbreak. , IVI and GeneOne held a ...
Breaking Medicine News(10 mins):
(Date:12/7/2016)... NEW YORK , December 7, 2016 ... Jazz Pharmaceuticals PLC (NASDAQ: JAZZ ), Anthera Pharmaceuticals ... DNAI ), and AveXis Inc. (NASDAQ: ... Biotechnology Sector Index fell roughly 37% to reach a level ... While it is down by approximately 14% for the year, ...
(Date:12/6/2016)... BROOKLYN, N.Y. , Dec. 6, 2016  Licenders is bringing ... . This new location in Park Slope at 203 13 th ... Brooklyn clientele. "Our goal is ... Our treatment plans are designed to get children right back to ... products are 100% all natural and safe for the whole family," ...
(Date:12/6/2016)... 6, 2016 Diabetes & Obesity Drug Development ... obesity disease cluster is currently dominated by therapeutics indicated ... diabetes mellitus (T2DM), and the majority of the pipeline, ... is attributable to these indications. While products indicated for ... there are a large number of these products in ...
Breaking Medicine Technology: