Study identified genetic mutations, pathway changes for lung cancer in never-smokers

Researchers have identified specific mutations and gene expression alterations that could lead to lung cancer in never-smokers, according to data presented at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine meeting in San Diego.

According to the study, never-smokers represent approximately 10% of patients with lung cancer in the United States, yet lung cancer remains one of the 10 most common causes of cancer mortality in never-smokers. Based on this evidence, researchers theorized that gene mutations and pathways — identified by whole-genome sequencing and whole-transcriptome sequencing — stimulate tumorigenesis in adenocarcinomas of never-smoker patients and could represent potential therapeutic targets.

Researcher completed whole-genome sequencing and whole-transcriptome sequencing on three female patients with lung adenocarcinomas: one never-smoker with advanced-stage disease, one never-smoker with early-stage disease and one smoker with early-stage disease. From the analysis, researchers found mutations in MAGEC1 — a tumor marker in melanoma and multiple myeloma — common between the early-stage, never-smoker tumor and the smoker tumor.

“This is the starting point. We certainly have a lot of pathways and gene expression alterations that we’re going to be very interested in confirming and looking at in larger cohorts of patients,” study researcher Timothy G. Whitsett, PhD, senior postdoctoral fellow in the cancer and cell biology division at the Translational Genomics Research Institute, said in a press release. “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 form of cancer.”

In addition, the study found that the early-stage, never-smoker patient contained a mutation in PIK3C3 and DOCK10, involved in cancer cell migration, and CSNK1E, involved in beta catenin-induced cancer cell proliferation. Analysis from the late-stage, never-smoker patient also exhibited a p53 mutation and a mutation in the DNA damage checkpoint gene, ATM.

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

For more information:

Whitsett TG. #A43. Presented at: AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine; Jan. 8-11, 2012; San Diego.

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