Discovery of new gene that protects against lung cancer

Nov 9 2004

Cancer Research UK scientists have discovered a new gene that protects against lung cancer, according to a study published in the journal PNAS.

The activity of the LIMD1 gene was reduced in all of the lung cancer samples the researchers tested, suggesting the gene plays an important role in stopping lung tumours developing.

Lung cancer is the biggest cause of cancer death in the UK, and it is notoriously difficult to treat.

Very little is known about the molecular basis of lung cancer. The team – based at University College London – believes LIMD1 may be an important piece in the puzzle, and hope their work may ultimately lead to new drugs to prevent and treat the disease.

The researchers also plan to investigate whether constituents of tobacco smoke could be partly responsible for damaging the LIMD1 gene.

LIMD1 is located on part of chromosome 3 called 3p21. Scientists have long suspected that 3p21 is home to important tumour suppressor genes, as it is missing in many types of cancers.

Professor Chris Boshoff, who heads the laboratory at the Wolfson Institute for Biomedical Sciences at University College London where the discovery was made, explains: "Cancer happens when genes that normally control cell growth are mutated, leading to uncontrolled proliferation.

"Tumour suppressor genes – as their name suggests – work to prevent tumours arising. Mutations in tumour suppressor genes stop them doing their job properly and so help cancer develop."

The research was funded by Cancer Research UK, with additional funding from the Wellcome Trust.

Chromosome region 3p21 is known to be missing in more than 90 per cent of lung tumours. The team's discovery that LIMD1 activity is reduced in most of the samples they tested is added evidence that LIMD1 mutations are important in lung cancer development.

The team found that mutations in LIMD1 were very common in lung cancer samples, strongly implicating the mutations in the development of cancer.

They also found that restoring LIMD1 function to lung cancer cells in mice significantly delayed tumour growth.

Professor Boshoff adds: "LIMD1 is a potential new target for scientists developing new therapies to combat lung cancer."

Dr Tyson Sharp, who led the research team at the Wolfson Institute, says: "We have found a new tumour suppressor gene. Our experiments suggest its loss may be an integral part of the development of lung cancer.

"Chromosome 3p is often deleted early in the development of lung cancer, which implies that inactivation of the LIMD1 gene could be a particularly important event in the early stages of lung cancer."

"Identifying mutations in key genes such as LIMD1 could enable earlier diagnosis of cancer, as they are early warning signs that something is going wrong."

Scientists will now look to see if cancer-causing toxins in tobacco leads to damage of chromosome 3p and subsequent LIMD1 inactivation.

Such a finding would be an invaluable step towards explaining how lung cancer develops.

Professor Robert Souhami, Cancer Research UK's Director of Policy and Communication, says: "Identifying the most important genetic mutations in each type of cancer is an important area of research. Scientists hope to design drugs to replace the function of mutated tumour suppressor genes.

"The team's findings offer a new target in the search for treatments for lung cancer."