Navigation Links
New type of genetic change identified in inherited cancer
Date:10/4/2009

DURHAM, N.C. Duke University Medical Center and National Cancer Institute scientists have discovered that a novel genetic alteration a second copy of an entire gene is a cause of familial chordoma, an uncommon form of cancer arising in bones and frequently affecting the nervous system.

Inherited differences in gene copy number, known as copy number variation (CNV), have been implicated in some hereditary diseases but none of the previously discovered familial cancer genes has had CNV as the genetic change.

"This alteration is unlike anything we have ever seen before in families that tend to develop the same kind of cancers," says Michael Kelley, M.D., an associate professor at Duke University Medical Center and senior author of the study appearing in Nature Genetics. "We are not talking about a mutation in a single gene, but the duplication of an entire gene. This discovery is a classic example of where science answers one question but raises many, many more."

Chordoma is rare, striking only one in every million people. But it is a devastating diagnosis. People who have the disorder typically develop tumors at the base of the skull, in the pelvis, or along the spinal column. The growths are thought to arise from remnants of the notochord, an embryonic precursor to spinal column. There are few treatments and no cure for chordoma; most who have the disease usually die within 10 years.

Kelley, chief of hematology and oncology at the Durham Veterans Affairs Medical Center, has been studying chordoma for years after a collaborator at the National Cancer Institute, Dilys Parry, a co-author of the study, discovered a family with a history of the disease spanning several generations. They concluded that there had to be some sort of inherited genetic defect at work. Parry conducted clinical studies that eventually identified six additional families with multiple relatives with chordoma.

Initial work focused on possible defects on chromosome 7, but no defect was found that was shared by all of those affected. Researchers conducted linkage studies that revealed six new areas in the genome where potential mutations were likely. But it wasn't until they used a technique called array comparative genomic hybridization, a method that allowed them to see structural changes in the genome in exquisite detail, that they were able to pinpoint the source of the culprit. They identified it as the T (Brachyury) gene on chromosome 6.

"Brachyury is a transcription factor that helps regulate the development of the notochord and we know the gene is overly active in the tumor tissue in many people with chordoma," says Kelley, "so we were pretty sure we were on to something."

Investigators screened 65 individuals (21 with chordoma) in seven families with a history of the disease, specifically looking for any alterations in the T gene. They discovered that all the patients with chordoma in four of the seven families had a second copy of the T gene. The duplication did not appear among members of the three other families, nor did it appear in 100 healthy, normal controls.

Kelley says investigators do not understand what Brachyury does to cause chordoma. Brachyury expression was found in tissue from chordomas not only in patients who had inherited the duplication but also in those who did not have the duplication.

"It is likely that other genes are at work here, or that some other mechanism we do not yet understand is in play. Based on our research, however, we do feel that it may be worthwhile to screen for complex genomic rearragements when trying to find the cause of familial cancers. It may be a more productive route than traditional gene-mapping methods."

Xiaohong Yang of the National Cancer Institute wrote the first draft of the paper, and along with David Ng, also of the NCI, analyzed the data. Ng, Sufeng Li, Kelly and David Alcorta, all of Duke, performed the laboratory studies including genotyping, sequencing and breakpoint evaluation. Parry, Ng, Eamonn Sheridan of St. James Hospital in Leeds, UK, and Norbert Liebsch, from Massachusetts General Hospital, identified and evaluated the chordoma families. Yang, Ng, Kelley, Parry and Alisa Goldstein planned the work and interpreted the results.


'/>"/>

Contact: Michelle Gailiun
michelle.gailiun@duke.edu
919-660-1306
Duke University Medical Center
Source:Eurekalert

Related medicine news :

1. Many Parents Share Genetic Test Findings With Kids
2. Genetic predisposition increases childhood asthma risk
3. New Alzheimers findings: High stress and genetic risk factor lead to increased memory decline
4. Test Spots Genetic Damage Done by Smoking
5. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
6. Scientists highlight benefits of genetic research in sport, but warn of ethical concerns
7. Genetics Hold Promise, Challenges for Cancer Care
8. Researchers genetically engineer micro-organisms into tiny factories
9. Study Questions Genetic Screening for Treatable Diseases
10. Researchers provide genetic associations from a genome-wide scan for cardiovascular disease traits
11. Genetic variation affects smoking cessation treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... (PRWEB) , ... June 27, ... ... in the patient payment industry today announced its strategic partnership with Connance, ... system workflows. , The two companies’ proven, proprietary technology combine to provide ...
(Date:6/26/2016)... California (PRWEB) , ... June 26, 2016 , ... Pixel ... Cut Pro X. , "Film editors can give their videos a whole new perspective ... Christina Austin - CEO of Pixel Film Studios. , ProSlice Levels contains over ...
(Date:6/25/2016)... ... , ... Austin residents seeking Mohs surgery services, can now turn to Dr. ... Russell Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization to include ... in Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction of Glenn ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has ... he has implemented orthobiologic procedures as a method for treating his patients. The ... first doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is ... associated with chronic pain and the benefits of holistic treatments, Serenity Recovery Center ... suffering with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 Roche (SIX: RO, ... clearance for its Elecsys BRAHMS PCT (procalcitonin) assay as ... or septic shock. With this clearance, Roche is the ... fully integrated solution for sepsis risk assessment and management. ... bacterial infection and PCT levels in blood can aid ...
(Date:6/23/2016)... , June 23, 2016 Research and ... News Issue 52" report to their offering. ... influenza treatment creates a favourable commercial environment for MedImmune to ... patient base that will serve to drive considerable growth for ... would serve to cap sales considerably, but development is still ...
(Date:6/23/2016)... PARK RIDGE, Ill. and INDIANAPOLIS ... caliber of students receiving a Lilly Diabetes Tomorrow,s Leaders ... hands. The 2016 scholarship winners, announced today online at ... refused to let type 1 diabetes stand in the ... Lilly Diabetes has supported the Foundation,s scholarship program since ...
Breaking Medicine Technology: