Navigation Links
Massive DNA search uncovers new mutations driving blood cancer
Date:12/12/2011

Public Images: Cut and paste into the body of the release.

SAN DIEGO -- The most comprehensive search to date of DNA abnormalities in chronic lymphocytic leukemia (CLL) has unearthed several new altered genes that drive this common blood cancer, a finding that could potentially help doctors predict whether an individual patient's disease will progress rapidly or remain indolent for years, say scientists from Dana-Farber Cancer Institute and the Broad Institute.

Using powerful "next-generation" DNA sequencing, the teams identified nine frequently mutated genes across 91 patients. Catherine J. Wu, MD, of Dana-Farber, a co-senior author of the report, says five of the mutated genes are implicated in CLL for the first time.

Wu says that mutations in one of the new genes, SF3B1, interfere with gene splicing, or "editing" of RNA messages that form a genetic template the cell uses to build a specified protein. "We have identified a new cancer pathway aberrant RNA splicing that has been underappreciated," says Wu, a researcher in Dana-Farber's Cancer Vaccine Center.

An advanced online publication has been scheduled for Dec. 12 by the New England Journal of Medicine, to coincide with a presentation of the results (abstract 463) at the American Society of Hematology's 2011 annual meeting on Monday, Dec. 12 at 10:30 a.m. PST.

The study's other two co-senior authors are Jennifer Brown, MD, PhD, of Dana-Farber and Brigham and Women's Hospital, and Gad Getz, PhD, of the Broad Institute, where the sequencing search was carried out.

CLL is the most common form of leukemia. The American Cancer Society expects it will be diagnosed in 14,570 patients in 2011, and projects 4,380 deaths. The behavior of the disease differs widely among patients. About half the time, CLL is aggressive, worsening steadily and rapidly, often with fatal outcomes. In many other patients, the leukemia is said to be "indolent," causing few symptoms for years or even decades. Doctors often choose not to treat the indolent form until symptoms become life-threatening.

Physicians have only a limited set of markers to predict the course of CLL in an individual, such as the presence of certain types of chromosome damage in the cancer cells, which are associated with more aggressive disease. Previous searches for predictive genetic clues spotted only a small number of "driver" mutations, but those hunts were limited in their power by the small number of tumor samples in the study.

The latest search harnessed Illumina sequencing technology at the Broad Institute to sequence leukemia and matched normal DNA samples from 91 patients with CLL, looking for frequently mutated genes in the tumors. They sequenced the entire genome in three patient samples, and only the protein-coding genes, collectively termed the "exome," in the other 88 patients.

The search turned up nine genes frequently mutated in the CLL samples, and these fell into five pathways regulating DNA damage repair, cell-cycle control, Notch signaling, inflammation, and RNA splicing/processing. Two had previously been associated with CLL and cancer in general. Another two mutations MYD88 and NOTCH1 were implicated in leukemia this year (2011). The remaining five, now identified for the first time as culprits in CLL, are SF3B1, FBXW7, DDX3X, MAPK1, and ZMYM3.

The SF3B1 gene was the second most commonly mutated gene, being found abnormal in 14 of the 91 leukemia DNA samples. The gene's full name is Splicing Factor 3b, subunit 1, and the protein it makes is part of the "spliceosome" a collection of proteins that govern the splicing out of extraneous RNA molecules ("introns") to create the RNA message ("exons"), or molecular recipe, from which the cell manufactures proteins for the body. "Defects in splicing have not previously been implicated in the biology of CLL," the researchers wrote.

The researchers checked to see whether CLL samples that contained the mutated genes also had specific deletions in chromosomes (the DNA structures that carry genes) previously known to signal a poor outlook in patients. They found that, indeed, the SF3B1 gene was often found in tandem with a particular chromosomal abnormality, consistent with a more aggressive form of CLL.

However, independent of the presence of the chromosomal deletion, the study revealed that a mutated SF3B1 gene by itself was a red flag for an aggressive case of CLL; patients harboring the mutant SF3B1 gene were more likely to need treatment sooner than individuals lacking the gene. Wu said that that the gene alteration might serve as a biomarker. Since these patients have more aggressive disease, knowledge of the presence of the gene alteration might prompt physicians early on to consider alternatives to conventional chemotherapy, such as earlier use of stem cell transplants to quell the disease.

The researchers said the study findings show the value of large-scale genome searches in elucidating cancers. The numerous genetic flaws uncovered by the search could not only aid in the prediction of disease course, they said, but also offer clues to the biological underpinnings of CLL, paving the way for novel targeted treatments.
'/>"/>

Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert  

Related medicine news :

1. New U of M start-up may save lives of victims of massive blood loss and trauma
2. Massive push to improve the health of women and children
3. Cargill Begins Massive Recall of Turkey Linked to Salmonella Outbreak
4. Landmark report reveals massive global cost of Alzheimers: 1 percent of global GDP -- and growing
5. Deadly effect of arsenic in drinking water measured in massive study
6. MovieHatch.com Offers Fame on Massive Times Square Billboard; New Contest Puts Winner's Face in Lights in Heart of Broadway
7. Infosolve Technologies Demonstrates OpenDQ's Massively Scalable Fuzzy Matching Capabilities on a Cloud Platform
8. Adult mortality trends reveal massive rise in global inequalities
9. Massive Food Flavoring Recall Underscores Need for New Tracking Technology to Contain Outbreaks of Foodborne Illness
10. Think Tank & Radio Network Encourage Massive Resistance to ObamaCare
11. United Nations Secretary-General Ban Ki-moon, President Bill Clinton, Launch MASSIVEGOOD, a Citizen Solution for Funding Global Health
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Massive DNA search uncovers new mutations driving blood cancer
(Date:5/27/2016)... ... May 27, 2016 , ... ... help educate the many who are unaware of the plight of aphasia. In ... run within the “Stroke Awareness” campaign. , The link between stroke and aphasia ...
(Date:5/27/2016)... ... May 27, 2016 , ... Aimed ... by inspiring human interest stories, courtesy of leaders in the nursing and health ... the industry, from leading advocates and associations—namely Jones & Bartlett Learning. , Jones ...
(Date:5/27/2016)... (PRWEB) , ... May 27, 2016 , ... ... in scholarships to students studying complementary medicine. Allison Outerbridge is this year’s ... her award on May 18 at the university’s Student Leadership Awards ceremony. , ...
(Date:5/26/2016)... ... , ... Despite last week’s media reports hinting at a June rate hike ... March 2017 for an interest rate increase, according to Rajeev Dhawan of the Economic ... Federal Open Market Committee (FOMC) dot charts are of interest to the press for ...
(Date:5/26/2016)... New Hampshire (PRWEB) , ... May 26, 2016 , ... ... skin care products, has been honored with a 2016 When Work Works Award for ... prestigious award, part of the national When Work Works project administered by the Families ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... , Germany and ... QIAGEN N.V. (NASDAQ: QGEN ; Frankfurt Prime ... a licensing and co-development agreement with Therawis Diagnostics GmbH to ... will be to develop and market PITX2 as a marker ... other high-risk breast cancer patients. "We are pleased ...
(Date:5/25/2016)... , May 25, 2016 ... & Expo earlier this month, the numbers and momentum ... continue to climb into the billions, more research and ... released 4th Edition State of Legal Marijuana Markets Report ... cannabis-focused data-analysis firm, much of the increase in sector ...
(Date:5/25/2016)... May 25, 2016 Inivata, ... precision of circulating tumour DNA (ctDNA) analysis to ... appointment of Professor Clive Morris as ... across the clinical development programme, scientific collaborations, and ... deliver significant improvements in clinical outcomes for patients. ...
Breaking Medicine Technology: