Featured Research

from universities, journals, and other organizations

Missing gene may drive more than one in four breast cancers

Date:
August 20, 2012
Source:
Cornell University
Summary:
More than one out of every four cases of breast cancer is associated with a specific, missing gene – a finding that could have significant implications for chemotherapy treatments, according a recent study.

More than one out of every four cases of breast cancer is associated with a specific, missing gene -- a finding that could have significant implications for chemotherapy treatments, according a recent study by Cornell University researchers.

The study shows that the lack of a certain gene occurs in almost 28 percent of human breast cancers, playing a role in some 60,000 breast-cancer cases in the United States and 383,000 worldwide this year. Posted online in the journal Genetics, the study has important clinical implications: It suggests that several existing drugs may be effective in treating breast cancers with the missing gene, called NF1. It also suggests that the commonly used breast cancer drug tamoxifen could make the disease worse in these specific cancers.

The NF1 gene negatively regulates one of the most important oncogenes -- genes that when mutated or expressed at high levels contribute to turning a normal cell into a cancerous one. This oncogene, called RAS, is involved in signaling inside the cell to control growth. When NF1 is missing or depleted, RAS becomes hyperactivated and can lead to tumor formation.

In the study, Cornell researchers used a mouse model with elevated mutation rates that led to breast cancer in 80 percent of the mice.

"These mice almost always get mammary tumors, and when we looked at their genomes, nearly all of them were missing this NF1 gene," said John Schimenti, professor of genetics at Cornell's College of Veterinary Medicine and the paper's senior author. "There are many big cancer studies that identify the most commonly mutated genes, but they don't prove experimentally that those genes are the drivers of cancer."

In humans, there are many causes of breast cancer, and each patient's cancer has a slightly different set of natural gene variants as well as new mutations in their tumors, so identifying individual genes that drive cancer can be problematic. But the model mice are inbred and get exactly the same tumor every time. "So we've eliminated all the noise," allowing the researchers to identify NF1 as a driver of these tumors, said Schimenti.

In the mouse model, RAS is hyperactivated. Since RAS is one of the most important oncogenes, many drugs have been already developed to interrupt the RAS pathway to treat cancer. "If NF1 is missing and it is causing cancer by activating RAS, then these drugs may help," said Schimenti. "Therefore, there doesn't need to be any more drug development to test this possibility right now."

The study also suggests that tamoxifen, one of the most common breast cancer treatments, may exacerbate the disease when the missing NF1 is the driver. Another study reported that NF1 protein depletion makes cancer cells resistant to tamoxifen, and tamoxifen-treated patients whose tumors have low NF1 levels had poorer clinical outcomes.

Schimenti and his colleagues plan to test whether they can reverse growth of tumors in mice missing the NF1 gene by inserting a replacement gene. They are also testing how effective RAS inhibitor drugs are at curbing cancer in mice. The paper shows that RAS inhibitors curb growth of these tumor cells in culture.

Marsha Wallace, a graduate student working in Schimenti's lab at Cornell, is the paper's lead author. Researchers from the University of North Carolina and Sloan Kettering Cancer Center co-authored the study.

The study was funded by the National Institutes of Health, the Empire State Stem Cell Fund, the National Cancer Institute and the Breast Cancer Research Foundation.


Story Source:

The above story is based on materials provided by Cornell University. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. D. Wallace, A. D. Pfefferle, L. Shen, A. J. McNairn, E. G. Cerami, B. L. Fallon, V. D. Rinaldi, T. L. Southard, C. M. Perou, J. C. Schimenti. Comparative Oncogenomics Implicates the Neurofibromin 1 Gene (NF1) as a Breast Cancer Driver. Genetics, 2012; DOI: 10.1534/genetics.112.142802

Cite This Page:

Cornell University. "Missing gene may drive more than one in four breast cancers." ScienceDaily. ScienceDaily, 20 August 2012. <www.sciencedaily.com/releases/2012/08/120820110736.htm>.
Cornell University. (2012, August 20). Missing gene may drive more than one in four breast cancers. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2012/08/120820110736.htm
Cornell University. "Missing gene may drive more than one in four breast cancers." ScienceDaily. www.sciencedaily.com/releases/2012/08/120820110736.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
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