Navigation Links
Sequence of ovarian genome identifies predominant gene mutations, points to possible treatment
Date:6/29/2011

HOUSTON -- (June 30, 2011) The genome of the most common form of ovarian cancer is characterized by a few common gene mutations but also surprisingly frequent structural changes in the genome itself, said members of The Cancer Genome Atlas (http://cancergenome.nih.gov/), including the Baylor College of Medicine (www.bcm.edu) Human Genome Sequencing Center (www.hgsc.bcm.tmc.edu/), that sequenced and analyzed more than 300 such tumors. The study was the first to achieve an overview of this type of ovarian cancer.

"We found that ovarian cancer has a dramatic pattern of genomic disruption," said Dr. Richard Gibbs (www.hgsc.bcm.tmc.edu/content-home-HGSC_director-x.hgsc) , director of the Baylor Human Genome Sequencing Center and an author of the report that appears in the current issue of the journal Nature (www.nature.com). The BCM Center completed one-quarter of the sequencing.

Ovarian carcinoma (a form of cancer) is the fifth leading cause of cancer deaths among women in the United States. An estimated 21,880 cases and 13,850 deaths from the disease occurred in 2010. More than 70 percent of patients are not diagnosed until they have an advanced stage form of the disease, and the most common kind of ovarian cancer is serous ovarian adenocarcinoma a high-grade form of which was sequenced by the researchers in this project. The National Cancer Institute (www.cancer.gov) and the National Human Genome Research Institute (http://www.genome.gov/) of the National Institutes of Health (www.nih.gov) funded this project.

The researchers said in their report that the spectrum of gene mutations in the study "was surprisingly simple."

The study found that 96 percent of the tumors had mutated TP53 genes. When normal, this gene is a tumor suppressor. Its loss allows tumors to develop without check. Nine other mutated genes occur at much lower but statistically significant rates. Among these are NF1, BRCA1, BRCA2, RB1, and CDK12. BRCA1 and BRCA2 (known primarily as breast cancer genes) that were mutated in 30 percent of patients while the occurrence of the other mutations was much lower. Some BRCA1 and BRAC2 mutations were inherited while others occurred spontaneously in the breast tissue.

"A globally disrupted genome is the common theme in this cancer," said Gibbs. "Large-scale amplifications and deletions of chromosome segments make this cancer very complex."

"This landmark study is producing impressive insights into the biology of this type of cancer," said National Institutes of Health Director Dr. Francis Collins. "It will significantly empower the cancer research community to make additional discoveries that will help us treat women with this deadly disease. It also illustrates the power of what's to come from our investment in The Cancer Genome Atlas."

While the mutation pattern seemed simple, the researchers found that, this form of ovarian cancer "demonstrates a remarkable degree of genomic disarray."

In particular, the authors point to the frequency of somatic copy number variations, in which parts of the genome are duplicated or deleted in the tumors themselves. More than half of these tumors had defects in genes that play a role in the repair of defects that occur when cells divide and duplicate their DNA. The authors said that drugs called PARP inhibitors are already used in this diseases and this explains why they are sometimes successful in treating the disease.

"We also defined a set of genes that were associated with worse or better patient outcome," said Dr. Chad Creighton (www.bcm.edu/cancercenter/index.cfm?pmid=9315), assistant professor in the division of biostatistics in the NCI-designated Dan L. Duncan Cancer Center (www.bcm.edu/cancercenter/) at BCM. He and others on the Genome Atlas team identified a transcriptional signature of 193 genes that predicts survival. (The transcriptional signature involves assessing gene activity by measuring the types and quantities of RNA [genetic material that forms a template from which parts of cell make protein] cells produce.) They correlated 108 genes with poor survival and 85 genes with good survival.

While high-grade serous ovarian adenocarcinoma is conventionally considered as one type of cancer having uniform features, "we could divide the tumors into four different groups based on gene expression patterns," said Creighton. "They look like four different cancers."

"We were able to define a set of genes that were associated with worse outcomes versus better outcomes in patients," he said. They applied this gene signature to other sets of data collected about ovarian cancer and found that the profile predicted worse or better outcome there as well.

"These data are all public," said Creighton. "They are meant for people to use to find specific genes for research. They could influence a lot of future studies."

The Cancer Genome Atlas project was created to provide this kind of information for a host of cancers some of which have already been sequenced and others underway or in the planning stages.

"This allows us to better characterize the disease at a molecular level and catalogue the genetic abberations," said Creighton. "This is a much more comprehensive dataset than we have ever had before."

"The new knowledge of the genomic changes in ovarian cancer has revealed that the molecular catalysts of this disease are not limited to small changes affecting individual genes," said NCI Director Dr. Harold E. Varmus. "Also important are large structural changes that occur in these cancer genomes. Cancer researchers can use this comprehensive body of information to better understand the biology of ovarian cancer and improve the diagnosis and treatment of this dreaded disease."


'/>"/>

Contact: Glenna Picton
713-798-4710
Baylor College of Medicine
Source:Eurekalert

Related medicine news :

1. Scientists sequence endangered Tasmanian devils genome
2. FDA could analyze public health consequences of its decisions better
3. Adult-supervised drinking in young teens may lead to more alcohol use, consequences
4. Entire T-cell receptor repertoire sequenced revealing extensive and unshared diversity
5. New Pediatrics study identifies the risks, consequences of video game addiction
6. Overexpression of repetitive DNA sequences discovered in common tumor cells
7. Scientists sequence gut microbes of premature infant
8. Neurons work like a chain of dominos to control action sequences
9. Of lice and man: Researchers sequence human body louse genome
10. New world Helicobacter pylori genome sequenced, dynamics of inflammation-related genes revealed
11. NHLBI to hold workshop on health consequences of sickle cell trait
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/5/2016)... ... 05, 2016 , ... As renowned, board-certified dermatologists, Dr. Sabrina G. Fabi and ... who do not do their research and undergo cosmetic dermatology treatments from unqualified practitioners ... of a renaissance and every other month a new treatment or device is launched, ...
(Date:12/5/2016)... , ... December 05, 2016 , ... ... called the CardioQuick Patch® significantly improves the reproducibility and accuracy of placing precordial ... healthcare settings. , Over the last 60 years, studies have shown that ...
(Date:12/4/2016)... ... 03, 2016 , ... While James Earl Jones is known for myriad roles ... show called "Front Page". One of the forthcoming episodes examines mammogram techniques; a very ... in large part due to early detection. Like any other disease, treatments have a ...
(Date:12/4/2016)... CA (PRWEB) , ... December 04, 2016 , ... ... without undergoing major cosmetic surgery can now take advantage of a cosmetic procedure ... advanced skin rejuvenation treatment that reduces the appearance of age spots, fine ...
(Date:12/2/2016)... ... ... Lori G. Cohen and Sara K. Thompson , shareholders in ... Conference Institute’s 21st Drug & Medical Device Litigation Conference , taking place in New ... Cohen, who chairs the firm’s Pharmaceutical, Medical Device & Health Care Litigation Practice and ...
Breaking Medicine News(10 mins):
(Date:12/4/2016)... innovative, personalized cell-based treatment for a high-risk form of the most common ... Hospital of Philadelphia today reported new results using ... The physician-scientists presented findings at the annual meeting of the American ... Continue Reading ... ...
(Date:12/2/2016)... , Dec 2, 2016 Research and Markets ... newsletter to their offering. ... , , R&D Drug ... Publishing,s proprietary R&D Drug Pipeline Database provides 24/7 online access to ... on the market and on investigational drug candidates in research & ...
(Date:12/2/2016)... Columbia , December 2, 2016 - bioLytical lanza el ... nuevas directrices de la OMS     Continue Reading ... ... , , ... enfermedades infecciosas, ha anunciado hoy que está expandiendo el lanzamiento de su INSTI ...
Breaking Medicine Technology: