Navigation Links
Study sheds new light on role of genetic mutations in colon cancer development
Date:6/7/2012

SEATTLE 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.


'/>"/>

Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
Source:Eurekalert

Related medicine news :

1. Two-Thirds of Osteo Hip Fractures Occur After 80: U.S. Study
2. Study links teamwork, communication with quality of nursing home care
3. HIV superinfection in Uganda may be more common than previously thought, study finds
4. Many Kids on Medicaid Dont See Dentist: Study
5. Reach2HD, a Phase II study in Huntingtons disease, launched
6. Belly Membrane May Regulate Immune System, Mouse Study Finds
7. Skin Cells Turned Into Brain Cells in Lab Study
8. Head-to-head study in RA shows that abatacept has comparable efficacy to adalimumab
9. Exercise Appears to Ease Nerve-Damage Pain in Rat Study
10. New Medicine Might Fight Drug-Resistant TB, Study Says
11. Exercise Controls Weight in White Girls Better Than in Black Girls: Study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... ... ... Digital Scientists, a software innovation lab specializing in web design and ... Carolina location. The lab has set up shop at the renowned NEXT Innovation ... Carolina clients for years from our office here in Atlanta,” explains Digital Scientists’ CEO, ...
(Date:3/24/2017)... Lake Orion, MI (PRWEB) , ... March 24, ... ... providing insurance assistance, financial planning, and related services to families and business owners ... charity initiative aimed at feeding regional families struggling with financial difficulties. , The ...
(Date:3/24/2017)... CA (PRWEB) , ... March 24, 2017 , ... ... on two panels at the Advanced ERISA Benefit Claims Litigation seminar in Chicago, ... Creating the Administrative Record, The majority of cases litigated under ERISA involve claims ...
(Date:3/24/2017)... , ... March 24, 2017 , ... ... first Certified Medical Reiki™ Master in Frederick, MD. Judy says, “I am passionate ... during what is often a very difficult and challenging time.” , A Certified ...
(Date:3/24/2017)... ... ... Adventures of Joey, The Dog Who Barks at Puddles”: a boisterous story about a ... God intended. “The Adventures of Joey, The Dog Who Barks at Puddles” is the ... writing, especially about truth and human behavior. , Published by Christian Faith Publishing, Patti ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... Tenn. , March 23, 2017  Provectus ... or the "Company"), a clinical-stage oncology and dermatology ... announced Definitive Financing Commitment Term Sheet (the "Definitive ... a group of the Company,s stockholders, who are ... Group" in a Form 8-K filed with the ...
(Date:3/23/2017)... 23, 2017 The key factors driving ... diabetic population, accelerating economic growth and increasing healthcare expenditure. Some ... higher life expectancy of ESRD patients, rising demand for home ... the expansion of the market is hindered by high treatment ... ...
(Date:3/23/2017)... 23, 2017 As a result of ... the prevalence of allergic diseases, cutting edge developments ... revolutionising the ways in which pharmaceutical and biotech ... promises to be both a high quality meeting ... interest groups, immunologists, research scholars and doctors. The ...
Breaking Medicine Technology: