Featured Research

from universities, journals, and other organizations

Sequence of ovarian genome identifies predominant gene mutations, points to possible treatment

Date:
June 29, 2011
Source:
Baylor College of Medicine
Summary:
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 that sequenced and analyzed more than 300 such tumors. The study was the first to achieve an overview of this type of ovarian cancer.

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, including the Baylor College of Medicine Human Genome Sequencing Center, 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, director of the Baylor Human Genome Sequencing Center and an author of the report that appears in the current issue of the journal Nature. The BCM Center completed one-quarter of the sequencing.

5th leading cause of cancer deaths

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 and the National Human Genome Research Institute of the National Institutes of Health 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) 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.

Very complex cancer

"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, assistant professor in the division of biostatistics in the NCI-designated Dan L. Duncan Cancer Center 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.

Gene expression patterns

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."

Cancer Genome Atlas

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."

Other Baylor researchers who took part in this work include Dr. David Wheeler, Kyle Chang, Huyen H Dinh, Jennifer A. Drummond, Dr. Gerald Fowler, Dr. Preethi Gunaratne, Alica C. Hawes, Christie L. Kovar, Lora R. Lewis, Margaret B. Morgan, Dr. Irene F. Newsham, Jireh Santibanez, Dr. Jeffrey G. Reid, Dr. Lisa R. Trevino, Dr. Yuan-Qing Wu, Dr. Min Wang and Donna M. Muzny.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bell et al. Integrated genomic analyses of ovarian carcinoma. Nature, 2011; 474 (7353): 609 DOI: 10.1038/nature10166

Cite This Page:

Baylor College of Medicine. "Sequence of ovarian genome identifies predominant gene mutations, points to possible treatment." ScienceDaily. ScienceDaily, 29 June 2011. <www.sciencedaily.com/releases/2011/06/110629132523.htm>.
Baylor College of Medicine. (2011, June 29). Sequence of ovarian genome identifies predominant gene mutations, points to possible treatment. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2011/06/110629132523.htm
Baylor College of Medicine. "Sequence of ovarian genome identifies predominant gene mutations, points to possible treatment." ScienceDaily. www.sciencedaily.com/releases/2011/06/110629132523.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins