New statistical analysis reveals thousands of rare mutations linked with cancer

April 20, 2017, Public Library of Science
A depiction of oncodomain hotspots found to be significantly overlapping with the active site of the protein kinase domain. Credit: Original image by Thomas A. Peterson, CC BY

Scientists have identified thousands of previously ignored genetic mutations that, although rare, likely contribute to cancer growth. The findings, which could help pave the way to new treatments, are published in PLOS Computational Biology.

Cancer arises when genetic in a cell cause abnormal growth that leads to a tumor. Some cancer drugs exploit this to attack tumor cells by targeting proteins that are mutated from their usual form because of mutations in the genes that encode them. However, only a fraction of all the mutations that contribute significantly to cancer have been identified.

Thomas Peterson, at the University of Maryland, and colleagues developed a new statistical analysis approach that uses genetic data from cancer patients to find cancer-causing mutations. Unlike previous studies that focused on mutations in individual genes, the new approach addresses similar mutations shared by families of related proteins.

Specifically, the new method focuses on mutations in sub-components of proteins known as domains. Even though different genes encode them, different proteins can share common protein domains. The new strategy draws on existing knowledge of protein domain structure and function to pinpoint locations within protein domains where mutations are more likely to be found in tumors.

Using this new approach, the researchers identified thousands of rare tumor mutations that occur in the same domain location as mutations found in other proteins in other tumors— suggesting that they are likely to be involved in cancer.

"Maybe only two patients have a mutation in a particular protein, but when you realize it is in exactly the same position within the as mutations in other proteins in cancer patients," says senior author of the study Maricel Kann, "you realize it's important to investigate those two mutations."

The researchers have coined the term "oncodomain" to refer to that are more likely to contain cancer-causing mutations. Further study of oncodomains could help inform drug development: "Because the domains are the same across so many proteins," Kann says, "it is possible that a single treatment could tackle cancers caused by a broad spectrum of mutated proteins."

Explore further: Novel mutation may be linked to prostate cancer in African American men

More information: Peterson TA, Gauran IIM, Park J, Park D, Kann MG (2017) Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. PLoS Comput Biol 13(4): e1005428.

Related Stories

Novel mutation may be linked to prostate cancer in African American men

February 23, 2017
Researchers have identified a novel mutation that may be associated with prostate cancer in African American men, according to a new study published in PLOS Computational Biology.

Probing proteins' 3-D structures suggests existing drugs may work for many cancers

June 13, 2016
Examining databases of proteins' 3-D shapes, scientists at Washington University School of Medicine in St. Louis have identified more than 850 DNA mutations that appear to be linked to cancer. The information may expand the ...

Discovery of genetic mutation may boost cancer therapies

February 24, 2017
A newly discovered type of genetic mutation that occurs frequently in cancer cells may provide clues about the disease's origins and offer new therapeutic targets, according to research from Weill Cornell Medicine and the ...

BRCA1 mutations in breast and ovarian cancer can predict treatment resistance

July 25, 2016
Mutations in the BRCA1 gene are one of the most common risk factors for breast and ovarian cancers. Although tumors that harbor BRCA1 mutations initially respond well to cancer treatments, many tumors eventually become less ...

Researchers see helpful protein causing cancer

February 9, 2016
Washington State University researchers have determined how a protein that helps cells fight viruses can also cause genetic mutations that lead to cancer.

Recommended for you

Cancer comes back all jacked up on stem cells

March 19, 2018
After a biopsy or surgery, doctors often get a molecular snapshot of a patient's tumor. This snapshot is important - knowing the genetics that cause a cancer can help match a patient with a genetically-targeted treatment. ...

A small, daily dose of Viagra may reduce colorectal cancer risk

March 19, 2018
A small, daily dose of Viagra significantly reduces colorectal cancer risk in an animal model that is genetically predetermined to have the third leading cause of cancer death, scientists report.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

Improved capture of cancer cells in blood could help track disease

March 15, 2018
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer - even though most free-floating cancer cells will not go on to establish a new tumor.


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.