Researchers map potential genetic origins, pathways of lung cancer in nonsmokers

January 9, 2012, The Translational Genomics Research Institute

Researchers at the Translational Genomics Research Institute (TGen) have begun to identify mutations and cellular pathway changes that lead to lung cancer in never-smokers -- a first step in developing potential therapeutic targets.

"This is the starting point. We certainly have a lot of pathways and alterations that we're going to be very interested in confirming and looking at in larger cohorts of patients," said Dr. Timothy G. Whitsett, Senior Postdoctoral Fellow in TGen's Cancer and Cell Biology Division.

Whitsett presented the findings today at the American Association for Cancer Research (AACR) and International Association for the Study of Lung Cancer (IASLC) Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine, held Jan. 8-11, 2012, at the San Diego Marriott Marina & Hotel.

"This is a very important subset of patients with lung cancer, and our research looks to identify pathways and genes that are potentially driving this cancer," said Dr. Whitsett, who works under Dr. Nhan Tran, head of TGen's CNS Tumor Research Lab. The title of the abstract Dr. Whitsett presented is Identification of key tumorigenic pathways in never-smoker lung adenocarcinoma patients using massively parallel DNA and RNA sequencing.

Never-smokers are defined for this study as individuals who smoked less than 100 cigarettes in their lifetime. About 10 percent of lung cancer cases occur in this patient population, which researchers have not examined as extensively as they have studied patients with lung cancer who smoked.

Whitsett and his colleagues looked at three female patients with adenocarcinoma: one never-smoker with early-stage disease; one never-smoker with late-stage disease; and, as a comparison, one smoker with early-stage disease. The team performed whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) on each patient to identify gene and pathway alterations that could have led to the development and progression of their specific lung cancer.

"In the never-smoker with early-stage cancer, there are very few mutations in the genome, but when we looked at the whole transcriptome, we see differences in gene expression," Whitsett said.

In the never-smoker with late-stage disease, researchers found mutations in what Whitsett called "classic tumor-suppressor genes." He and his colleagues hypothesize that mutations of the tumor-suppressor genes might be a factor in late-stage lung cancer in never-smokers.

Notably, the researchers reported that these never-smokers' tumors lacked alterations in common genes associated with such as EGFR, KRAS and EML/ALK translocations. This finding makes these ideal cases for the discovery of new mutations that may drive lung adenocarcinomas in never-smokers, according to the researchers.

Whitsett said that using WGS and WTS to identify cancer origins "has become a way to really dive down into an individual tumor to try to understand the pathways that may be driving that tumor and identify what therapeutic interventions may be possible."

The researchers are now validating these findings in about 30 never-smokers with lung adenocarcinoma and about 60 clinically matched with lung adenocarcinoma.

Explore further: Lung tumors in never-smokers show greater genomic instability than those in smokers

Related Stories

Lung tumors in never-smokers show greater genomic instability than those in smokers

July 5, 2011
Lung adenocarcinomas in people who have never smoked show greater genome instability than those in smokers, supporting the theory that lung cancer in never smokers arises through different pathways, according to research ...

First whole-genome lung cancer study set for conference

July 6, 2011
A first-of-its-kind study of a patient with lung cancer who never smoked will be presented today by TGen and the Virginia G. Piper Cancer Center at Scottsdale Healthcare at the 14th World Conference on Lung Cancer, July 3-7 ...

Gene fusion in lung cancer afflicting never-smokers may be target for therapy

December 22, 2011
Smoking is a well-known risk factor for lung cancer, but nearly 25% of all lung cancer patients have never smoked. In a study published online today in Genome Research, researchers have identified a previously unknown gene ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.