Lung cancer is a leading cause of cancer-related death globally. Researchers at the McDonnell Genome Institute and collaborators are investigating the mutational burden, spectrum of mutation and affected genes in lung cancer tumors.
Lung cancer is a leading cause of cancer-related death globally. Lung cancer often has a relatively low survival rate that is attributed, in part, to the fact that it is routinely diagnosed at later stages. So it is necessary to develop new and effective means of prevention and treatment for this deadly disease.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. While smoking causes most cases of lung cancer, approximately 10-40% of patients diagnosed with lung cancer report no history of tobacco smoking. Researchers at the McDonnell Genome Institute and collaborators are using whole genome sequencing of tumor and adjacent normal tissue and transcriptome sequencing of tumor samples from 17 patients with NSCLC to investigate the mutational burden, spectrum of mutation, and affected genes in lung cancer tumors and how they differ between smokers and non-smokers (Govindan et al. Cell, 2012). Analyses of these genomes have identified mutations in genes not previously reported in lung cancer, as well as recurrent lung cancer mutations. They have observed marked differences between the tumor genomes of smokers and non-smokers, including an increase in mutation frequency in smokers, varying types of mutations, and specific genes affected. Studies such as these that use comprehensive genomic analysis contribute to the understanding of the molecular genetics of cancer and the development and application of therapy.
Squamous cell lung cancer, or carcinoma, is responsible for about 400,000 deaths each year. It is linked to smoking and responsible for 30 percent of all lung cancer cases. The McDonnell Genome Institute is involved in a nationwide consortium that reported on the first comprehensive genetic analysis of this form of cancer. The work is part of The Cancer Genome Atlas that seeks to describe the genetics of common tumors with the goal of improving prevention, detection and treatment. The study examined the tumor and normal tissue of 178 patients with lung squamous cell carcinoma. The investigators found recurring mutations common to many patients in 18 genes. Many of these mutations can be targeted with existing drugs. And almost all of the tumors showed mutations in a gene called TP53, known for its role in repairing damaged DNA. The researchers also noted that lung squamous cell carcinoma shares many mutations with head and neck squamous cell carcinomas, supporting the emerging body of evidence that cancers may be more appropriately classified by their genetics rather than the primary organ they affect. Current treatment for squamous cell lung cancers includes chemotherapy and radiation, but there are no drugs specifically designed to target this particular type of lung cancer.