Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Study Identifies Novel Genomic Changes in the Most Common Type of Lung Cancer

Published: Thursday, July 10, 2014
Last Updated: Thursday, July 10, 2014
Bookmark and Share
TCGA finds mutations in a key cancer-causing pathway, expanding targets for existing drugs.

Researchers from The Cancer Genome Atlas (TCGA) Research Network have identified novel mutations in a well-known cancer-causing pathway in lung adenocarcinoma, the most common subtype of lung cancer.

Knowledge of these genomic changes may expand the number of possible therapeutic targets for this disease and potentially identify a greater number of patients with treatable mutations because many potent cancer drugs that target these mutations already exist.

TCGA is jointly funded and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health. A TCGA analysis of another, less common, form of lung cancer, squamous cell carcinoma, was reported in 2012.

In this new study, published online July 9, 2014, in the journal Nature, researchers examined the genomes, RNA, and some protein from 230 lung adenocarcinoma samples. In three-quarters of the samples, the scientists ultimately identified mutations that put a cell signaling pathway known as the RTK/RAS/RAF pathway into overdrive.

"The integrated nature of TCGA analysis made these findings and their potential therapeutic implications possible," said NIH Director Francis S. Collins, M.D., Ph.D. "We hope this lays the groundwork for future work in precision medicine."

Mutations affecting the RTK/RAS/RAF pathway can cause it to become stuck in the "on" state. As a result, signals that promote cancer cell proliferation and survival are produced continuously. However, some drugs currently available curb aberrant activity of this pathway and prompt therapeutic responses in patients.

"Combined with the earlier TCGA analysis of squamous lung cancers, we now have a comprehensive understanding of many of the genetic pathways that lead to cancers of the lung," said NCI Director Harold Varmus, M.D. "Based on this knowledge, we can now seek better pathway inhibitors to improve patient outcomes. However, for the time being, stopping smoking or never starting remain the most reliable ways to reduce the number of deaths due to lung cancer."

In the group's initial scan of tumor samples, researchers identified gene mutations that would increase RTK/RAS/RAF pathway activity in 62 percent of the samples. The affected genes are oncogenes, or genes that have the potential to cause cancer when mutated or expressed at high levels. Consequently, these tumor samples were classified as oncogene-positive.

To identify additional alterations, the investigators looked at DNA copy number changes, or changes in gene number resulting from the deletion or amplification (multiplication) of sections of DNA in the genome. In doing so, they detected amplification of two oncogenes, ERBB2 and MET, which are part of the RTK/RAS/RAF pathway. Gene amplification usually leads to increased expression of the encoded protein in cells.

Now that these amplifications have been identified, clinicians may be able to treat patients whose tumors have specific gene changes with drugs currently available or under development.

"It is quite striking that we have now identified an actionable mutation in over 75 percent of patients with lung adenocarcinoma, a significant improvement from a decade ago," said Matthew Meyerson, M.D., Ph.D., Harvard Medical School, Dana-Farber Cancer Institute, The Broad Institute, and one of the lead investigators on the project.

Additional analysis identified other genes that may play important roles in lung cancer development. Mutations in one of these genes, NF1, had previously been reported in lung cancer; NF1 is a known tumor suppressor gene that regulates the RTK/RAS/RAF pathway. Mutations in NF1 also put the pathway into overdrive. Another mutated gene, RIT1, is also part of the RTK/RAS/RAF pathway, and this is the first study to associate mutation of this gene with lung cancer.

"This most recent TCGA study again demonstrates the power, depth and breadth of TCGA data," said NHGRI Director Eric Green, M.D., Ph.D. "These results give us important new genomic insights into the development and behavior of an important form of cancer."

In the aggregate, the several forms of lung cancer comprise the most common cause of cancer-related deaths worldwide, with more than 1 million deaths annually. NCI estimates that only 17.5 percent of people diagnosed with lung cancer are still alive five years later.

Lung adenocarcinoma, the most common form of the disease in the United States, develops in tissues near the outer parts of the lungs and can spread widely. Although smoking is the main risk factor, adenocarcinoma is also the most common type of lung cancer among lifelong non-smokers and the risk of lung cancer is increased by 20 percent to 30 percent by exposure to secondhand smoke.

In addition to the two lung cancer studies, the TCGA Research Network has generated data and published analyses on a number of cancers, all of which can be found on the TCGA website, ( TCGA-generated data are freely available at the TCGA Data Portal and CGHub .

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Cellular Factors that Shape the 3D Landscape of the Genome Identified
Researchers have identified 50 cellular factors required for the proper 3D positioning of genes by using novel large-scale imaging technology.
Tuesday, August 18, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
Tuesday, July 21, 2015
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
NCI-MATCH Trial will Link Targeted Cancer Drugs to Gene Abnormalities
Precision medicine trial will open to patient enrollment in July.
Tuesday, June 09, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Lipid Nanoparticle Therapeutic Treats Ebola in Monkeys
A newly designed agent was effective in treating monkeys infected with a deadly Ebola virus strain.
Wednesday, May 06, 2015
Possible Treatment for Lethal Pediatric Brain Cancer
NIH-funded preclinical study suggests epigenetic drugs may be used to treat leading cause of pediatric brain cancer death.
Tuesday, May 05, 2015
NIH Study Finds Genetic Link for Rare Intestinal Cancer
Researchers recommend screening for people with family history.
Friday, April 17, 2015
Novel Approach Gives Insights Into Tumor Development
Scientists used a powerful new technique to turn off all the genes in mouse lung cancer cells and test how they affect tumor growth and metastasis.
Tuesday, March 24, 2015
Strengthening the Immune System’s Fight Against Brain Cancer
NIH-funded research suggests novel way to improve vaccine efficacy in brain tumors.
Friday, March 20, 2015
Range of Molecular Alterations in Head and Neck Cancers Uncovered
TCGA tumor genome sequencing analyses offer new insights into the effects of HPV and smoking, and find genomic similarities with other cancers.
Thursday, January 29, 2015
Scientific News
Revolutionary Technologies Developed to Improve Outcomes for Lung Cancer Patients
Breath test to detect lung cancer brings oxygen directly to the wound.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Nanocarriers May Carry New Hope for Brain Cancer Therapy
Berkeley lab researchers develop nanoparticles that can carry therapeutics across the brain blood barrier.
RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
University of Glasgow Researchers Make An Impact in 60 Seconds
Early-career researchers were invited to submit an engaging, dynamic and compelling 60 second video illuminating an aspect of their research.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
CRISPR-Cas9 Gene Editing: Check Three Times, Cut Once
Two new studies from UC Berkeley should give scientists who use CRISPR-Cas9 for genome engineering greater confidence that they won’t inadvertently edit the wrong DNA.

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos