Navigation Links
Study sheds new light on role of genetic mutations in colon cancer development

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
Fred Hutchinson Cancer Research Center

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:
(Date:10/13/2017)... ... October 13, 2017 , ... Dickinson Insurance and Financial ... financial preparation services, is providing an update on a charitable event that began ... Rescue is a locally recognized nonprofit that provides shelter and care for animals ...
(Date:10/13/2017)... IL (PRWEB) , ... October 13, 2017 , ... ... which established the certification process to promote standards of excellence for the field ... Symposium, scheduled for March 22 – 25, 2018 in Orlando, Florida at the ...
(Date:10/13/2017)... ... October 13, 2017 , ... Apple Rehab Shelton Lakes ... a mock evacuation of the facility as part of a disaster drill on October ... Hose EMS and Shelton City Emergency Manager, as well as the Connecticut Long ...
(Date:10/13/2017)... ... 2017 , ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out ... free event, sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting ... children of all ages; it is a non-competitive, non-timed event, which is all about ...
(Date:10/13/2017)... ... 2017 , ... “The Journey: From the Mountains to the Mission Field”: the ... in the Philippines. “The Journey: From the Mountains to the Mission Field” is the ... She has taught all ages and currently teaches a class of ladies at her ...
Breaking Medicine News(10 mins):
(Date:9/25/2017)... 2017  EpiVax, Inc., a leader in the ... today announced the launch of EpiVax Oncology Inc., ... therapeutic cancer vaccines. EpiVax has provided $500,000 in ... enabling technologies to the new precision immunotherapy venture. ... Oncology as Chief Executive Officer. Gad brings over ...
(Date:9/22/2017)... -- As the latest Obamacare repeal effort moves is debated, ... and Lindsey Graham (R-SC) medical device market ... is in an odd place.  The industry wants repeal ... on medical device sales passed along with the Affordable ... visits and hospital customers with the funding to invest ...
(Date:9/19/2017)... a venture-backed medical device company developing a non-invasive, robotically assisted, platform therapy that uses pulsed ...   ... Jim Bertolina, ... Tom Tefft ... medical device executive Josh Stopek , PhD, who has led R&D and business development ...
Breaking Medicine Technology: