Featured Research

from universities, journals, and other organizations

Previously held beliefs about the role of genetic mutations in colon cancer development challenged

Date:
June 7, 2012
Source:
Fred Hutchinson Cancer Research Center
Summary:
In exploring the genetics of mitochondria – the powerhouse of the cell – researchers have stumbled upon a finding that challenges previously held beliefs about the role of mutations in cancer development. For the first time, researchers have found that the number of new mutations are significantly lower in cancers than in normal cells.

In exploring the genetics of mitochondria -- the powerhouse of the cell -- researchers at Fred Hutchinson Cancer Research Center have stumbled upon a finding that challenges previously held beliefs about the role of mutations in cancer development.

For the first time, researchers have found that the number of new mutations are significantly lower in cancers than in normal cells.

"This is completely opposite of what we see in nuclear DNA, which has an increased overall mutation burden in cancer," said cancer geneticist Jason Bielas, Ph.D., whose findings are published in the June 7 issue of PLoS Genetics.

Mutations are changes in the genetic sequence of a cell's genome and can occur as a result of environmental exposure to viruses, radiation and certain chemicals, or due to spontaneous errors during cell division or DNA replication.

Mitochondria, which are primarily responsible for the cell's energy production, are semi-autonomous; similar to the nucleus, they have their own set of DNA, which encodes genes critical for the functioning of the cell. While the role of genomic instability has been well characterized in nuclear DNA, this is the first attempt to determine whether instability in mitochondrial DNA may play a similar role in cancer growth and metastasis.

"We were surprised to find that the frequency of new mutations in mitochondrial DNA from tumor cells is decreased compared to that of normal cells," said Bielas, an assistant member of the Public Health Sciences and Human Biology divisions at the Hutchinson Center. "By extension, this suggests, somewhat counterintuitively, that higher mitcochondrial mutation rates may actually serve as a barrier to cancer development, and drugs that focus directly on increasing mitochondrial DNA damage and mutation might swap cancer's immortality for accelerated aging and tumor-cell death."

For the study, the researchers used using an ultra-sensitive test to detect mutations in mitochondrial DNA from normal and cancerous colon tissue resected from 20 patients prior to chemotherapy.

Bielas and colleagues first set out to analyze mutation rates in mitochondrial DNA because they wanted to see if it could act as a surrogate for nuclear DNA as a cancer biomarker. "Cells contain a thousandfold more mitochondrial genetic material than nuclear DNA, so theoretically you'd need a thousand times less tissue to get the same genetic information to predict clinical outcomes such as how fast a tumor would progress or whether it would be resistant to therapy," Bielas said.

While mitochondrial DNA proved to be an unreliable stand-in for nuclear DNA as a cancer biomarker, it offers promise as a new drug target.

"If we could increase DNA damage and mutation within the mitochondrial genome, theoretically we could decrease cancer," Bielas said. "That's what we're testing now. This is a whole new hypothesis."

The way mitochondria maintain genetic stability in the face of cancer, Bielas suggests, may be because unlike normal cells, cancer cells do not need oxygen to survive. In fact, cancer cells decrease the process by which they get energy from the mitochondria and rely instead on a process called glycolysis, which is a form of energy production in the absence of oxygen. "We believe less damage occurs to mitochondrial DNA of cancer cells because they no longer need oxygen," he said. "If we could program a cancer cell to once again need oxygen, we expect it would die -- with minimal side effects."

Bielas and colleagues are now testing this theory in the laboratory, seeing whether cancer cells that are reprogrammed to utilize oxygen and/or are targeted for mitochondrial DNA damage respond better to certain therapeutic agents.

"This finding is a game-changer because it challenges previous notions about the role of mutations in cancer development," said Bielas, who is also an affiliate assistant professor of pathology at the University of Washington, where the ultra-sensitive mutation-detection technology, called Random Mutation Capture, was developed. The test is so sensitive that it can detect the mutational equivalent of one misprinted letter in a library of a thousand 1,000-page books.

"This work started with the idea that there would be a huge mutation burden in the mitochondrial DNA, but our findings were completely opposite of what we had expected. Hopefully our discovery will open up new avenues for treatment, early detection and monitoring treatment response of colon cancer and other malignancies," he said.

The National Institute of Environmental Health Sciences, the Ellison Medical Foundation and Fred Hutchinson Cancer Research Center funded this research. Collaborators included researchers at the University of Washington, the University of North Carolina, and St. Vincent's University Hospital in Dublin, Ireland.


Story Source:

The above story is based on materials provided by Fred Hutchinson Cancer Research Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nolan G. Ericson, Mariola Kulawiec, Marc Vermulst, Kieran Sheahan, Jacintha O'Sullivan, Jesse J. Salk, Jason H. Bielas. Decreased Mitochondrial DNA Mutagenesis in Human Colorectal Cancer. PLoS Genetics, 2012; 8 (6): e1002689 DOI: 10.1371/journal.pgen.1002689

Cite This Page:

Fred Hutchinson Cancer Research Center. "Previously held beliefs about the role of genetic mutations in colon cancer development challenged." ScienceDaily. ScienceDaily, 7 June 2012. <www.sciencedaily.com/releases/2012/06/120607175809.htm>.
Fred Hutchinson Cancer Research Center. (2012, June 7). Previously held beliefs about the role of genetic mutations in colon cancer development challenged. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2012/06/120607175809.htm
Fred Hutchinson Cancer Research Center. "Previously held beliefs about the role of genetic mutations in colon cancer development challenged." ScienceDaily. www.sciencedaily.com/releases/2012/06/120607175809.htm (accessed August 27, 2014).

Share This




More Health & Medicine News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WHO Calls for Ban on E-Cigarette Sales to Minors

WHO Calls for Ban on E-Cigarette Sales to Minors

AFP (Aug. 26, 2014) The World Health Organization called Tuesday on governments should ban the sale of e-cigarettes to minors, warning that they pose a "serious threat" to foetuses and young people. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Newsy (Aug. 26, 2014) A study published in the journal "Neurology" interviewed more than 19,000 people and found 15 percent suffer from being "sleep drunk." Video provided by Newsy
Powered by NewsLook.com
Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Newsy (Aug. 26, 2014) A new study found fewer deaths from prescription drug overdoses in states that have legalized medical marijuana. But experts disagree on the results. Video provided by Newsy
Powered by NewsLook.com
Official: British Ebola Sufferer Receiving Experimental Drug

Official: British Ebola Sufferer Receiving Experimental Drug

AFP (Aug. 26, 2014) A British nurse infected with Ebola while working in Sierra Leone is being given the same experimental drug used on two US missionaries who have recovered for the disease, doctors in London say. Duration: 00:44 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:
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