Translate
Translate this website into the following languages:



Close Tab
Donations
UC San Diego Health
menu iconMenu
search iconSearch

New Gene Fusions and Mutations Linked to Gastrointestinal Stromal Tumors

Findings could lead to additional targeted treatments for more patients

December 15, 2016  |  

​In recent years, researchers have identified specific gene mutations linked to gastrointestinal stromal tumors (GIST), which primarily occur in the stomach or small intestine, with 5,000 to 6,000 new cases per year in the United States.

But 10 to 15 percent of adult GIST cases and most pediatric cases lack the documented tell-tale mutations, making identification and treatment more difficult. In their paper published online Dec. 14 in the Journal of Translational Medicine, researchers at University of California San Diego School of Medicine and Moores Cancer Center have identified new gene fusions and mutations associated with this subset of GIST patients.

“We are continuing to slice the GIST pie into thinner pieces based upon identifying new driver genes,” said Jason Sicklick, MD, associate professor of surgery at UC San Diego School of Medicine and surgical oncologist at Moores Cancer Center at UC San Diego Health. “This will allow for a more personalized approach to treating GIST patients.”

Sicklick and colleagues are leading efforts to diagnose and treat GIST, which originates in special cells that signal muscles to contract, moving food and liquid through the digestive system. Many current therapies for GIST are ineffective in patients whose tumors lack mutations in the classic oncogenic drivers of GIST. Ultimately, more than 95 percent of patients eventually succumb to drug-resistant GIST, highlighting the necessity for alternative therapeutic targets.

Treatment with imatinib (marketed as Gleevec) has proven effective in many GIST cases associated with KIT oncogene mutations, the most common driver of the disease. Building upon that success and approach, Sicklick’s team, which included collaborators in Oregon, Texas, Massachusetts, Pennsylvania, Florida and South Korea, used broad genomic sequencing of GIST patients without KIT or other documented mutations to identify alterations in at least two new genes: FGFR1 and NTRK3. “Broad genomic sequencing was critical to expand our search beyond the KIT mutations streetlight,” said Olivier Harismendy, PhD, head of the oncogenomics laboratory at Moores Cancer Center, referring to observational bias of previous studies.

“These findings provide novel insights into the biology of the disease and new potential genetic drivers,” Sicklick said. “With further studies, we can build an even more complete genetic profile of GIST, which in turn can lead to new individualized treatments and better outcomes for more GIST patients. For example, one patient in this study had an ETV6-NTRK3 mutant GIST and responded to a matched therapy with Loxo-101, a highly selective TRK inhibitor, after progressing on several earlier lines of FDA-approved therapies for GIST.”

Co-authors of the study include Eileen Shi, Chih-Min Tang, Katherine E. Fero, James D. Murphy, Paul T. Fanta, Martina De Siena, Adam M. Burgoyne, Lisa Madlensky, Gregory M. Heestand, and Razelle Kurzrock, UC San Diego Moores Cancer Center; Juliann Chmielecki, Kai Wang, Siraj M. Ali, Deborah Morosini, and Jeffrey S. Ross, Foundation Medicine Inc.; Michael C. Heinrich, Portland VA Health Care System; Guhyun Kang, and Christopher L. Corless, Oregon Health Sciences University; David Hong, University of Texas MD Anderson Cancer Center; Sujana Movva, Fox Chase Cancer Center; and Jonathan C. Trent, University of Miami Sylvester Cancer Center.

Funding for this research came, in part, from the National Institutes of Health (KL2 RRO31978, R21 CA177519, R21 CA192072, P30 CA023100, U54 HL108460, K08 CA168999, R21 CA192072, P30 CA023100), GIST Cancer Research Fund and Life Raft Group, Veterans Administration Review grant and Joan and Irwin Jacobs Fund.


​Care at UC San Diego Health

Cancer

Gastrointestinal Cancers



Media Contact

Jackie Carr
858-249-0456
jcarr@ucsd.edu

Share This Article


Related News

10/4/2016
Physician-scientists with Moores Cancer Center at UC San Diego Health have been leading the way in pancreatic cancer care by investigating new therapies as well as offering innovative clinical trials ...
10/4/2016
Many types of cancer become drug resistant, making them difficult to treat. Researchers with University of California San Diego School of Medicine and Moores Cancer Center have identified a strategy t ...
2/1/2016
Twenty-two University of California, San Diego scientists and physicians are among the 2015 listing of “The World’s Most Influential Scientific Minds,” an annual compendium of “Highly Cited Researcher ...
9/28/2015
A collaborative program aimed at reducing the burden of cancer among Hispanic/Latinos in San Diego and Imperial counties through research and community outreach has received a $13 million grant from t ...



Follow Us

Our bimonthly newsletter delivers healthy lifestyle tips, patient stories and research discovery news. Subscribe: