Featured Research

from universities, journals, and other organizations

Mutations in one gene can cause many cancers, study shows

Date:
March 30, 2010
Source:
Ohio State University Medical Center
Summary:
An important gene that normally protects the body from cancer can itself cause a variety of cancers depending on the specific mutation that damages it. People who inherit a mutated copy of the PTEN gene have Cowden syndrome, a condition that carries a high risk of cancer in organs such as the breast, thyroid and ovary. This study linked specific mutations in the gene to distinct kinds of cancer in organs targeted by the syndrome.

An important gene that normally protects the body against cancer can itself cause a variety of cancers depending on the specific mutation that damages it, according to a new study by investigators at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).

Related Articles


The study examined mutations in a gene called PTEN. People who inherit a mutated copy of this gene have Cowden syndrome, a condition that carries a high risk of cancer in a number of organs, including the breast, thyroid and ovary. In addition, PTEN is frequently mutated in normal body cells leading to prostate, lung and pancreatic cancers.

Why people with Cowden syndrome develop different cancers, or cancers that are more severe in some than in others, is unknown, though the cause is often attributed to the natural genetic differences that exist between individuals.

This animal study, however, linked specific mutations in the gene to distinct kinds of cancer in organs targeted by the syndrome.

"We showed that the mutations themselves play a critical role in driving the cancers that occur in certain organs in people with Cowden syndrome," says principal investigator Gustavo Leone, associate professor of molecular virology, immunology and medical genetics at the OSUCCC-James.

"Together, our findings demonstrate that specific inherited PTEN mutations have a strong influence in the variable predisposition to cancer of patients with Cowden syndrome."

The findings, published in the March 16 issue of the Proceedings of the National Academy of Sciences of the United States of America, suggest that testing for specific PTEN mutations might predict the kind and severity of cancer that will develop in people with the syndrome.

Furthermore, because PTEN is the second most commonly mutated gene in human cancer overall, the same mutations might predict severity in sporadic tumors, as well.

"Mutations in this gene also play a role in developmental disabilities and perhaps in autism, so this mouse model might be useful for studies in those conditions, as well," says co-principal investigator Michael Ostrowski, professor and chair of molecular and cellular biochemistry at Ohio State.

For this study, Leone, Ostrowski and their colleagues developed three strains of genetically identical mice, each of which had one of three specific PTEN mutations found in people with Cowden syndrome. This left each strain with a different version of the PTEN protein. The study showed that each version functioned in a different way, and each influenced cancer development to a different degree.

Mutation 1 disabled the protein altogether and often caused cancer in the animals, while mutation 2 produced a protein that was more active than the normal PTEN protein, and sometimes caused cancer. Mutation 3 altered the protein in ways that should have made it more cancer-causing but also made it more fragile, so less of the protein was present to cause problems. This mutation sometimes didn't cause cancer at all.

Using a database of more than 400 patients with Cowden syndrome, the researchers found that patients with these same mutations have cancer in the corresponding organs as the mice. The mice also showed equivalent gender differences in tumor development, with females developing more thyroid tumors, and males developing more adrenal gland and stomach tumors.

The researchers are now investigating why patients may experience differences in cancer severity even when they have the same mutation.

Funding from the National Cancer Institute, the American Cancer Society, the Susan Komen Foundation, the Evelyn Simmers Foundation, and the U.S. Department of Defense supported this research.

Leone is the recipient of the Pew Charitable Trusts Scholar Award and the Leukemia and Lymphoma Society Scholar Award.


Story Source:

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


Journal Reference:

  1. H. Wang, M. Karikomi, S. Naidu, R. Rajmohan, E. Caserta, H.-Z. Chen, M. Rawahneh, J. Moffitt, J. A. Stephens, S. A. Fernandez, M. Weinstein, D. Wang, W. Sadee, K. La Perle, P. Stromberg, T. J. Rosol, C. Eng, M. C. Ostrowski, G. Leone. Allele-specific tumor spectrum in Pten knockin mice. Proceedings of the National Academy of Sciences, 2010; 107 (11): 5142 DOI: 10.1073/pnas.0912524107

Cite This Page:

Ohio State University Medical Center. "Mutations in one gene can cause many cancers, study shows." ScienceDaily. ScienceDaily, 30 March 2010. <www.sciencedaily.com/releases/2010/03/100329203545.htm>.
Ohio State University Medical Center. (2010, March 30). Mutations in one gene can cause many cancers, study shows. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2010/03/100329203545.htm
Ohio State University Medical Center. "Mutations in one gene can cause many cancers, study shows." ScienceDaily. www.sciencedaily.com/releases/2010/03/100329203545.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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