Nav: Home

New gene fusions and mutations linked to gastrointestinal stromal tumors

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" says 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."
-end-
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.

University of California - San Diego

Related Disease Articles:

Findings support role of vascular disease in development of Alzheimer's disease
Among adults who entered a study more than 25 years ago, an increasing number of midlife vascular risk factors, such as obesity, high blood pressure, diabetes, high cholesterol and smoking, were associated with elevated levels of brain amyloid (protein fragments linked to Alzheimer's disease) later in life, according to a study published by JAMA.
Dietary factors associated with substantial proportion of deaths from heart disease, stroke, and disease
Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the US in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.
Study links changes in oral microbiome with metabolic disease/risk for dental disease
A team of scientists from The Forsyth Institute and the Dasman Diabetes Institute in Kuwait have found that metabolic diseases, which are characterized by high blood pressure, high blood sugar, and obesity -- leads to changes in oral bacteria and puts people with the disease at a greater risk for poor oral health.
Fatty liver disease contributes to cardiovascular disease and vice versa
For the first time, researchers have shown that a bi-directional relationship exists between fatty liver disease and cardiovascular disease.
Seroprevalence and disease burden of chagas disease in south Texas
A paper published in PLOS Neglected Diseases led by researchers at the National School of Tropical Medicine at Baylor College of Medicine suggests that the disease burden in southern Texas is much higher than previously thought.
Maternal chronic disease linked to higher rates of congenital heart disease in babies
Pregnant women with congenital heart defects or type 2 diabetes have a higher risk of giving birth to babies with severe congenital heart disease and should be monitored closely in the prenatal period, according to a study published in CMAJ.
Citrus fruits could help prevent obesity-related heart disease, liver disease, diabetes
Oranges and other citrus fruits are good for you -- they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy.
Gallstone disease may increase heart disease risk
A history of gallstone disease was linked to a 23 percent increased risk of developing coronary heart disease.
New disease gene will lead to better screening for pediatric heart disease
Cardiomyopathy, or a deterioration of the ability of the heart muscle to contract, generally leads to progressive heart failure.
Early weight loss in Parkinson's disease patients may signify more serious form of disease
A study led by a Massachusetts General Hospital investigator finds evidence of an association between weight loss in patients with early Parkinson's disease and more rapid disease progression.

Related Disease Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...