Nav: Home

Gene mutations cause leukemia, but which ones?

February 23, 2017

Kevin Watanabe-Smith, Ph.D., likens cell mutations to typos in text messages.

"Mutations are part of life. They are mistakes in a gene like typos in a text message," said Watanabe-Smith, a postdoctoral fellow with the OHSU Knight Cancer Institute. "But which mutations cause cancer? That's the real question. And this problem is impossible to understand without a strong model system to test those mutations."

Watanabe-Smith's research, published today in the journal Oncotarget, sought to better understand one "typo" in a standard leukemia assay, or test. While studying cancer biology and completing his doctorate in the lab of Brian Druker, M.D., at the OHSU Knight Cancer Institute, Watanabe-Smith encountered a new problem: an issue with the model system itself.

"When I was sequencing the patient's DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn't put there. And I was getting different mutations every time," said Watanabe-Smith.

He decided to formally study this phenomenon with his lab advisers, who included Druker; Cristina Tognon, Ph.D., scientific director, Druker lab; and Anupriya Agarwal, Ph.D., assistant professor of hematology & medical oncology, OHSU School of Medicine; researcher with the OHSU Knight Cancer Institute, all co-authors on the paper.

"Kevin and team would sequence the DNA, just to make sure the mutation's still there, and in that process they would pick up additional mutations that we didn't put there in the gene we were looking at," said Tognon. "After we saw this in several cases we knew it was worth further study."

His initial research, identifying and characterizing a growth-activating mutation in a patient with T-cell leukemia, was first published last April in the journal Leukemia. The research published today was focused on better understanding the lab's model system, to ensure that future researchers trying to identify cancer-causing mutations are using accurate and reproducible methods.

Their research investigates a common cell line assay, used since the 1980's, to detect which mutations are important in driving leukemia and other cancers. They found this assay is prone to a previously unreported flaw, where the cells, called Ba/F3 cells, can acquire additional mutations.

"The potential impact is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible," Watanabe-Smith said. "Then we had the question: 'Did the cells transform because of a mutation the patient had, or did they transform because these new mutations they managed to pick up somewhere?'"

Ultimately, he says, the research team recommends an additional step in the Ba/F3 assay (sequencing outgrown cell lines) to improve reproducibility of future results. While the results urge further research, the message to scientific community is clear: There seems to be more potential for problems than previously anticipated in this standard assay.

"We're using this method to advance our understanding of patients' cancers. I now have a better idea of what may be contributing to this patient's leukemia and potentially what drugs could be used to control it. It will hopefully help the next person with the same mutation," Watanabe-Smith said.
-end-
Particulars: Watanabe-Smith is an Achievement Rewards for College Scientists (ARCS) scholar. Druker is a Howard Hughes Medical Institute Investigator.

Oregon Health & Science University

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Uncounted
First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at Radiolab.org/donate.