Gene changes identified in lung cancer

Lung cancer is the most common cause of cancer deaths in the US and throughout the world. Like all cancers, lung adenocarcinoma arises from errors in DNA that lead to uncontrolled cell growth. Identifying the changes in each cancer’s complete set of DNA, its genome, may ultimately result in more targeted therapies, improved prevention, and new detection strategies.

The Cancer Genome Atlas (TCGA) Research Network is a comprehensive effort to analyse the molecular basis of cancer. With more than 150 scientists at dozens of institutions across the nation, the TCGA research network is funded by NIH’s National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI). In a new TCGA study, researchers examined tumour samples and matched normal material from 230 patients with lung adenocarcinoma. The study recently appeared online in Nature.

In 143 out of 230 samples (62 per cent), the researchers found known activating mutations (misspellings) in oncogenes, genes known to have the potential to cause cancer when mutated or expressed at high level. To identify additional alterations, the investigators looked at DNA copy number changes, changes in gene number from the deletion or multiplication (amplification) of sections of DNA. They detected amplification of two oncogenes, ERBB2 and MET, that are part of a signaling pathway known as RTK/RAS/RAF. These mutations cause the pathway to become stuck in the “on” state, triggering tumour cell growth and survival.

The researchers also identified mutations in other genes, including NF1 and RIT1, part of the RTK/RAS/RAF pathway, that can drive lung adenocarcinomas.

By analysing DNA, RNA, and protein levels, the team determined that several metabolic pathways were activated in the tumour samples. Overall, 76 per cent of the samples had mutations that activate the RTK/ RAS/ RAF pathway. This work may lead to refinements in how cancers are classified and could lead to more personalised diagnosis and treatment.

EP News Bureau – Mumbai