New genetic fault linked to lung cancer in non-smokers

In collaboration with the Press Association

Korean scientists have discovered a gene fault that may be behind thousands of cases of lung cancer worldwide, particularly in non-smokers.

The research, published in the journal Genome Research, could underpin the development of future tailored treatments for these patients.

Although smoking is responsible for most lung cancers, nearly one quarter of all lung cancer patients have never smoked.

Using gene sequencing technology, the team from Seoul National University in South Korea found a previously unknown gene fault caused by two separate genes being joined together - a so-called 'gene fusion' - in a case of lung adenocarcinoma on a 33-year-old man who had never smoked and had no history of cancer in his family.

The group sequenced and compared the genome of the patient's cancer and normal tissue, but found no faults in genes that were already known to be associated with lung cancer, such as EGFR, KRAS, and EML4-ALK mutations.

The researchers also analysed the RNA molecules inside the patient's cancer cells. RNA acts as a messenger carrying instructions from DNA to control the production of proteins. Analysing RNA can reveal gene rearrangement events that are difficult to detect by DNA sequencing and which may be causing the cancer.

From the RNA sequencing analysis, the researchers built a list of possible mutations and narrowed it down to a single gene fusion that could be a cancer-causing event.

The scientists found that two previously separate genes called KIF5B and RET had fused to form a hybrid gene in the lung tumour cells.

When the team looked at 20 other people with lung cancer, they found that two of them also had the gene fusion in their tumour, indicating that the fusion event is relatively common.

The report's authors predict that the KIF5B-RET fusion occurs in about six per cent of all lung adenocarcinoma cases.

"We showed that genome sequencing technology could reveal a previously hidden cause of human cancer, which can be used as a therapeutic target for personal cancer therapy," said the report's senior author Dr Jeong-Sun Seo.

They concluded the fault is likely to be a promising target for treatment, but that further epidemiological studies are needed to more accurately define how often the KIF5B-RET gene fusion occurs in lung cancers.

Professor Siow-Ming Lee, a Cancer Research UK lung cancer specialist at the University College London Cancer Institute and Hospitals, said the work was at an early stage, but could represent the first step towards developing a new targeted treatment for some lung cancers.

He also said: "Tobacco is responsible for the vast majority of lung cancers, but non-smokers can also develop the disease, and the cause of many such cases remains unknown.

"If it is confirmed that around 6 per cent of lung adenocarcinomas have this gene fusion, then thousands of people around the world may benefit from any future treatment developed to target this abnormal gene.

"We've already started to personalise treatment for lung cancer patients - for example, drugs like gefitinib, erlotinib and crizotinib work best in patients with specific tumour gene faults. This work is yet another step towards an era of more precise and targeted cancer treatment."

Copyright Press Association 2011

References

  • Ju, Y., Lee, W., Shin, J., Lee, S., Bleazard, T., Won, J., Kim, Y., Kim, J., Kang, J., & Seo, J. (2011). Fusion of KIF5B and RET transforming gene in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing Genome Research DOI: 10.1101/gr.133645.111