Gene responsible for many spontaneous breast cancers identified

October 2, 2012, Genetics Society of America

Cancerous tumors contain hundreds of mutations, and finding these mutations that result in uncontrollable cell growth is like finding the proverbial needle in a haystack. As difficult as this task is, it's exactly what a team of scientists from Cornell University, the University of North Carolina, and Memorial Sloan-Kettering Cancer Center in New York have done for one type of breast cancer. In a report appearing in the journal Genetics, researchers show that mutations in a gene called NF1 are prevalent in more than one-fourth of all noninheritable or spontaneous breast cancers.

In mice, NF1 mutations are associated with hyper-activation of a known cancer-driving protein called Ras. While researchers have found earlier evidence that NF1 plays a role in other types of cancer, this latest finding implicates it in . This suggests that the drugs that inhibit Ras activity might prove useful against breast cancers with NF1 mutations.

"As we enter the era of personalized medicine, genomic technologies will be able to determine the molecular causes of a woman's breast cancer," said John Schimenti, Ph.D., a researcher involved in the work from the Center for Vertebrate Genomics at Cornell University College of Veterinary Medicine in Ithaca, New York. "Our results indicate that attention should be paid to NF1 status in , and that drug treatment be adjusted accordingly both to reduce the cancer and to avoid less effective treatments."

To make this discovery, scientists analyzed the genome of that arise in a mouse strain prone to genetic instability—whose activity closely resembles the activity in human —looking for common mutations that drive tumors. The gene NF1 was missing in 59 out of 60 tumors, with most missing both copies. NF1 is a suppressor of the oncogene Ras, and Ras activity was extremely elevated in these tumors as a consequence of the missing . Researchers then examined The Cancer Genome Atlas (TCGA) data, finding that NF1 was missing in more than 25 percent of all human breast cancers, and this was associated with a decrease in NF1 gene product levels, which in turn is known to increase Ras activity.

"This research is compelling because it helps us understand why some breast cancers are more likely to respond to only certain types of treatment," said Mark Johnston, Editor-in-Chief of the journal Genetics. "The findings reported in this article may guide clinicians to better treatments specific to the needs of each patient."

Explore further: Gene deletion drives more than a quarter of breast cancers

More information: Marsha D. Wallace, Adam D. Pfefferle, Lishuang Shen, Adrian J. McNairn, Ethan G. Cerami, Barbara L. Fallon, Vera D. Rinaldi, Teresa L. Southard, Charles M. Perou, and John C. Schimenti Comparative Oncogenomics Implicates the Neurofibromin 1 Gene (NF1) as a Breast Cancer Driver, Genetics, October 2012 192:385-396

Related Stories

Gene deletion drives more than a quarter of breast cancers

August 15, 2012
A new 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.

Pediatric tumors traced to stem cells in developing brain

July 9, 2012
Stem cells that come from a specific part of the developing brain help fuel the growth of brain tumors caused by an inherited condition, researchers at Washington University School of Medicine in St. Louis report.

New study identifies novel role for PEA-15 protein in cancer growth

November 21, 2011
A new study from the University of Hawaii Cancer Center reveals that PEA-15, a protein previously shown to slow ovarian tumor growth and metastasis, can alternatively enhance tumor formation in kidney cells carrying a mutation ...

Recommended for you

New approach attacks 'undruggable' cancers from the outside in

January 23, 2018
Cancer researchers have made great strides in developing targeted therapies that treat the specific genetic mutations underlying a patient's cancer. However, many of the most common cancer-causing genes are so central to ...

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.