Featured Research

from universities, journals, and other organizations

Study finds new genetic error in some lung cancers

Date:
October 27, 2013
Source:
Dana-Farber Cancer Institute
Summary:
Scientists report on a gene fusion that spurs the cells to divide rapidly. Treating the cells with a compound that blocks the protein caused the cells to die which may offer a targeted therapy in patients.

A fine-grained scan of DNA in lung cancer cells has revealed a gene fusion -- a forced merger of two normally separate genes -- that spurs the cells to divide rapidly, scientists at Dana-Farber Cancer Institute and the University of Colorado Cancer Center report in a new paper in the journal Nature Medicine. Treating the cells with a compound that blocks a protein encoded by one of those genes -- NTRK1 - caused the cells to die.

Related Articles


The finding suggests that the fusion of NTRK1 to other genes fuels the growth of some lung adenocarcinomas (a form of non-small cell lung cancer), and that drugs that target NTRK1's protein product could be effective in patients whose lung tumors harbor such fusions.

"Treatment with targeted therapies is now superior to standard chemotherapy for many patients with lung cancers that harbor genetic changes including those with fusions involving the gene ALK," says Pasi A. Jänne, MD, PhD, of Dana-Farber, the senior co-author of the paper with Robert C. Doebele, MD, PhD, of CU Cancer Center. "We know of several other genes that are fused in lung cancer and that offer attractive targets for new therapies. Our discovery places lung adenocarcinomas with NTRK1 fusions squarely within that group."

In the study, researchers performed next-generation DNA sequencing tests -- which read the individual elements of the genetic code over long stretches of chromosomes -- on tumor samples from 36 patients with lung adenocarcinomas whose tumors did not contain any previously known genetic alterations that could be found with standard clinical tests. In two of those samples -- both from women who had never smoked -- investigators found that a key region of the NTRK1 gene had become fused to normally distant genes (to the gene MPRIP in one patient; and the gene CD74 in the other).

NTRK1 holds the blueprint for a protein called TRKA, which dangles from the surface of cells and receives growth signals from other cells. The binding of NTRK1 to other genes causes TRKA to issue cell-growth orders on its own, without being prompted by outside signals.

In the laboratory, investigators mixed NTRK1-inhibiting agents into lung adenocarcinoma cells harboring NTRK1 fusions. The result was a dampening of TRKA's activity and the death of the cancer cells.

Investigators then designed a new test using fluorescence in situ hybridization (FISH) to detect NTRK1 fusions and tested an additional 56 tumor samples. In total, three of 91 tumor samples which had no other sign of cancer-causing genetic abnormalities, had fusions involving NTRK1.

"These findings suggest that in a few percent of lung adenocarcinoma patients -- people in whose cancer cells we had previously been able to find no genetic abnormality -- tumor growth is driven by a fusion involving NTRK1," Jänne says. "Given that lung cancer is a common cancer, even a few percent is significant and translates into a large number of patients. Our findings suggest that targeted therapies may be effective for this subset of lung cancer patients."

"This is still preclinical work," Doebele says, "but it's the first -- and maybe even second and third -- important steps toward picking off another subset of lung cancer with a treatment targeted to the disease's specific genetic weaknesses."


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Aria Vaishnavi, Marzia Capelletti, Anh T Le, Severine Kako, Mohit Butaney, Dalia Ercan, Sakshi Mahale, Kurtis D Davies, Dara L Aisner, Amanda B Pilling, Eamon M Berge, Jhingook Kim, Hidefumi Sasaki, Seung-il Park, Gregory Kryukov, Levi A Garraway, Peter S Hammerman, Julia Haas, Steven W Andrews, Doron Lipson, Philip J Stephens, Vince A Miller, Marileila Varella-Garcia, Pasi A Jänne, Robert C Doebele. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nature Medicine, 2013; DOI: 10.1038/nm.3352

Cite This Page:

Dana-Farber Cancer Institute. "Study finds new genetic error in some lung cancers." ScienceDaily. ScienceDaily, 27 October 2013. <www.sciencedaily.com/releases/2013/10/131027185029.htm>.
Dana-Farber Cancer Institute. (2013, October 27). Study finds new genetic error in some lung cancers. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2013/10/131027185029.htm
Dana-Farber Cancer Institute. "Study finds new genetic error in some lung cancers." ScienceDaily. www.sciencedaily.com/releases/2013/10/131027185029.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins