In a world first, scientists at Washington University, US, have sequenced the entire genome of a woman with acute myelogenous leukaemia (AML). They sequenced DNA from both normal skin cells and malignant tumour cells and found that 10 genes were mutated in the cancerous cells. The findings were published in the journal Nature.
The study found mutations in two genes that were previously known to be associated with AML. Eight of the mutations, however, have not been previously linked with the cancer. They also examined the DNA from tumour cells of 187 other AML patients, but found that none had any of the eight new mutations.
It is currently thought that a cell becomes cancerous after accumulating mutations throughout its life, each one pushing the cell towards uncontrolled malignant growth. Nine of the 10 mutations in this patient's case were found in all tumour cells, the tenth was only in some tumour cells, so it is possible that this mutation occurred last; the tipping point that caused the cancer.
Dr Richard Wilson, lead researcher of the study, said: 'We found mutations in genes that make a lot of sense when normal cells become cancer cells. That they seem to be fairly unique to this particular patient says on the one hand that this is a complicated disease'. He added that 'the complications validate our approach - we have to look at a number of patients to see not only what is different but what they have in common'. Further research is now underway to sequence the whole genome of another AML patient.
The technology for genome sequencing has become cheaper and more efficient since it was developed. When the first human genome sequence was completed in 2003, it had taken years and cost millions of pounds. Now, a human genome can be sequenced in months for a fraction of the cost. The researchers in Washington used a new technique called massively parallel sequencing. Although they sequenced the patient's entire genome, they only analysed mutations in the DNA sequences that produce proteins, an estimated 1 to 2 per cent of the human genome. To find mutations in other regions, known as intergenic DNA, will require further intensive analyses.
Understanding which mutations lead a cell to become cancerous can help scientists discover the underlying mechanisms of the disease, and open up avenues for discovering new treatments. In addition, understanding an individual's genetic basis of cancer could lead to highly personalised treatments.