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Lung cancer tumours in smokers have 10-times more genetic mutations

By Adrian Bishop - 13 Sep 2012 16:0:0 GMT
Lung cancer tumours in smokers have 10-times more genetic mutations

Lung cancer image; Credit: © Shutterstock

Smokers who have lung cancer suffer 10-times more genetic mutations in tumours than non-smokers with the disease, a new study shows.

The findings of the research, from the Washington University School of Medicine in St. Louis, USA, have just been published in the journal Cell.

Senior author Richard K. Wilson, PhD, who is director of The Genome Institute at Washington University, says, "None of us were surprised that the genomes of smokers had more mutations than the genomes of never-smokers with lung cancer. But it was surprising to see 10-fold more mutations. It does reinforce the old message - don't smoke."

The study identified around 3,700 mutations in 17 patients suffering from non-small cell lung cancer, which is the most common type. All but five of them were smokers.

In each non-smoker, the researchers discovered at least one mutated gene that is able to be treated with drugs currently available for other diseases or through clinical trials. In all patients, they found 54 mutated genes linked with existing drugs.

First author Ramaswamy Govindan, MD, an oncologist who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University, says, "Whether these drugs will actually work in patients with these DNA alterations still needs to be studied.

"But papers like this open up the landscape to understand what's happening. Now we need to drill deeper and do studies to understand how these mutations cause and promote cancer, and how they can be targeted for therapy."

There are two types of lung cancer - small cell and non-small cell. Around 85% of all cases are non-small cell and they are split into three more classifications. This current study examined two of them - adenocarcinoma - that was linked to 16 patients and large-cell carcinoma that one patient had.

Ramaswamy Govindan, who is national co-chair of the lung cancer group, and Richard K Wilson also took part in a bigger genomic study of 178 patients with the third type, squamous cell carcinoma, which was recently detailed in the journal Nature and was part of The Cancer Genome Atlas project that aims to describe the genetics of common cancers.

Ramaswamy Govindan says, "Over the next year or so, we will have studied nearly 1,000 genomes of patients with lung cancer, as part of The Cancer Genome Atlas. So we are moving in the right direction - toward future clinical trials that will focus on the specific molecular biology of the patient's cancer."

Taking into account emerging genetic research demonstrating common mutations in different cancer types, Richard K Wilson suggests there may come a point when doctors can label and treat a tumour based on the mutated genes rather than the affected organ.

Lung cancer might be called EGFR cancer, after the mutated gene that drives the growth of the tumour. Mutations in EGFR have been discovered in different cancers, such as lung, breast and colon.

The labeling is relevant as targeted therapies are approved based upon the diseased organ or tissue. Herceptin®, for example, is basically a breast cancer drug, but Richard K Wilson has seen lung cancer patients with mutations in the same gene that is targeted by Herceptin.

"For example, if genome sequencing revealed that a lung cancer patient has a mutation known to be sensitive to a drug that works in breast tumours with the same genetic alteration, you may want to use that agent in those lung cancer patients, ideally as part of a clinical trial," Richard K Wilson says.

"In the coming years, we hope to be treating cancer based more on the altered genetic make-up of the tumour than by the tissue of origin."

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Topics: Smoking / Lung Disease / Cancer