Scientists complete "groundbreaking" analyses of lung cancer and melanoma genomes

In collaboration with the Press Association

The Wellcome Trust Sanger Institute has announced the first comprehensive analyses of the genomes of lung cancer and melanoma skin cancer.

Published in Nature, the studies reveal all of the mutations that are present in the genomes of these two cancers.

The researchers analysed tissue samples taken from a lung cancer patient and a malignant melanoma patient using powerful new DNA sequencing technologies.

They then compared these genome sequences with those obtained by analysing each patient's normal tissue, enabling them to identify any changes that were specific to the cancer.

More than 23,000 mutations were found in the lung cancer genome - approximately one mutation for every 15 cigarettes smoked, according to the researchers - while the melanoma genome had more than 33,000 mutations.

Professor Mike Stratton, from the Cancer Genome Project at the Wellcome Trust Sanger Institute, pointed out that lung cancer and melanoma skin cancer are two cancers for which the main risk factors are known - smoking in the case of lung cancer and exposure to UV radiation for skin cancer.

"With these genome sequences, we have been able to explore deep into the past of each tumour, uncovering with remarkable clarity the imprints of these environmental mutagens on DNA, which occurred years before the tumour became apparent," he revealed.

"We can also see the desperate attempts of our genome to defend itself against the damage wreaked by the chemicals in cigarette smoke or the damage from ultraviolet radiation," he continued.

"Our cells fight back furiously to repair the damage, but frequently lose that fight."

The next step will be to find out which of the mutations actually cause cancer.

It may also be possible to produce a complete genome catalogue for individual patients which would inform treatment decisions.

As Dr Peter Campbell from the Wellcome Trust Sanger Institute explained, "The knowledge we extract over the next few years will have major implications for treatment.

"By identifying all the cancer genes, we will be able to develop new drugs that target the specific mutated genes and work out which patients will benefit from these novel treatments."

Professor Carlos Caldas, a cancer genomics expert from Cancer Research UK's Cambridge Research Institute, said the research was groundbreaking.

"Like molecular archaeologists, these researchers have dug through layers of genetic information to uncover the history of these patients' disease. What's so new in this study is the researchers have been able to link particular mutations to their cause.

"By repeating and refining this technique with other forms of cancer, and comparing the results to data from the Human Genome Project, the hope and excitement for the future is that we'll eventually have a detailed picture of how different cancers develop, and ultimately how better to treat and prevent them."

Harpal Kumar, Cancer Research UK's chief executive, added: "This fascinating work shows that great progress is being made to understand a lot more about how cancer develops. It shows in precise detail, and for the first time, the huge impact that smoking has in triggering the development of lung cancer, as well as the extent of the damage caused by UV radiation in relation to melanoma.

"The next step will be to find out which of these thousands of mutations are just 'collateral damage' and which actually drive these cancers. Only then can we begin to find ways to correct or prevent them.

"Cancer Research UK is extremely encouraged by this fast-emerging area of research. Never before has the potential of genomics to bring benefits to patients been so apparent, and we are already planning major new investments to add further depth to this cutting-edge work."

References

  • Pleasance, E. et al (2009). A comprehensive catalogue of somatic mutations from a human cancer genome Nature DOI: 10.1038/nature08658
  • Pleasance, E. et al (2009). A small-cell lung cancer genome with complex signatures of tobacco exposure Nature DOI: 10.1038/nature08629