Skip Ribbon Commands
Skip to main content
Translate
Donations
menu iconMenu
search iconSearch

Gene Mutation Found for Aggressive Form of Pancreatic Cancer

Discovery may prove useful in future diagnoses and in developing new therapies

May 27, 2014  |  

Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma (ASC) tumors – the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer.

The findings are published in the May 25 advance online issue of Nature Medicine.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with roughly 45,220 new cases diagnosed and more than 38,400 deaths annually. Both numbers are rising. ASC cases are infrequent, but typically have a worse prognosis than more common types of pancreatic cancer.

“There has been little progress in understanding pancreatic ASC since these aggressive tumors were first described more than a century ago,” said co-senior author Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine. “One problem has been identifying mutations unique to this class of tumors.”

In their paper, Wilkinson, co-senior author Yanjun Lu, PhD, of Tongji University in China, and colleagues report that ASC pancreatic tumors have somatic or non-heritable mutations in the UPF1 gene, which is involved in a highly conserved RNA degradation pathway called nonsense-mediated RNA decay or NMD. It is the first known example of genetic alterations in an NMD gene in human tumors.

NMD has two major roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) – molecules that help transcribe genetic information into the construction of proteins essential to life. Second, it degrades a specific group of normal mRNAs, including those encoding proteins promoting cell growth, cell migration and cell survival. Loss of NMD in these tumors may “release the brakes on these molecules, and thereby driving tumor growth and spread,” said Wilkinson.

Co-first author Rachid Karam, MD, PhD, a postdoctoral fellow in Wilkinson’s laboratory said the findings will create new opportunities for the development of novel diagnostic approaches and therapeutic strategies for targeting pancreatic cancer. “Currently, pancreatic cancer is detected far too late in most cases for effective treatment, and therapeutic options are limited,” Karam said.

Co-authors include Chen Liu, Fang Su, GuoTong Xu, LiXia Lu, ChongRen Wang, MeiYi Song, JingPing Zhu, YiRan Wang and YiFan Zhao, Tongji University School of Medicine; YingQi Zhou and Gang Li, Second Military Medical University; Yuan Ji, Fudan University; Wai Chin Foo, Mingxin Zuo and Milind Javie, University of Texas MD Anderson Cancer Center.

Funding for this research came, in part, from The National Key Basic Research Program of China, the National Natural Science Foundation of China and the National Institutes of Health.

# # #

Media contact: Scott LaFee, 619-543-6163, slafee@ucsd.edu


Related Specialties

Cancer



Media Contact

Related News

5/21/2015
Using human embryonic stem cells, researchers at University of California, San Diego School of Medicine and Moores Cancer Center and Sanford-Burnham Medical Research Institute created a model that all ...
5/8/2015
Therapies that specifically target mutations in a person’s cancer have been much-heralded in recent years, yet cancer cells often find a way around them. To address this, researchers at University of ...
5/1/2015
Researchers at UC San Diego School of Medicine conducted the first population-based study that characterizes the association and temporal relationship between gastrointestinal stromal tumors (GIST) an ...
5/1/2015
In proof-of-concept experiments, researchers at University of California, San Diego School of Medicine demonstrate the ability to tune medically relevant cell behaviors by manipulating a key hub in ce ...
4/29/2015
Researchers at University of California San Diego School of Medicine report pancreatic cancer rates are highest in countries with the least amount of sunlight. Low sunlight levels were due to a combin ...
4/20/2015
Researchers at the University of California, San Diego School of Medicine and Moores Cancer Center have discovered a molecular mechanism that connects breast tissue stiffness to tumor metastasis and p ...
10/23/2014
In a push to further speed clinical development of emerging stem cell therapies, Sanford Stem Cell Clinical Center at UC San Diego Health System was named today one of three new “alpha clinics” by the ...
10/20/2014
UC San Diego Sanford Stem Cell Clinical Center is pushing therapeutic stem cell-based science out of the laboratory and closer to real-world medical applications. The unprecedented trials involve pote ...


Share This Article



Follow Us