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Leukaemia patient's genome sequence pinpoints gene mutations in other patients

10 August 2009

By Adam Fletcher

Appeared in BioNews 520

The second complete cancer cell genome sequence was published online last week in the New England Journal of Medicine, representing a pioneering effort to comprehensively describe the hundreds of genetic changes that underlie this most insidious of diseases. The work was carried out by researchers at Washington University's Genome Center and the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, US. The same team was behind the first whole cancer genome sequence published in the journal Nature just ten months ago.

Researchers sequenced the genome of a tumour cell from a 38-year old man with Acute Myeloid Leukaemia (AML), and compared it to the sequence from a healthy skin cell from the same patient. Any differences in the two sequences were flagged and analysed. Amazingly, none of the mutations identified in this study are the same as those reported in the previous publication - also an AML patient - demonstrating the astonishing diversity of cancers. 'Only by sequencing thousands of cancer genomes are we going to find and make sense of the complex web of genetic mutations and the altered molecular pathways in this disease', explained lead author Dr Elaine Mardis.

This time, the team identified some 750 AML-associated mutations. Twelve of these were within Genes, whilst 52 were in the poorly understood non-coding stretches that lie in-between genes. To corroborate their findings, Mardis and colleagues also looked at sequences from a further 187 AML patients. Four of these mutations turned up again and again, including a novel change in a gene called IDH1, a mutation already associated with a form of brain cancer called a glioma. When mutations are shared by different patients in this way, it is probable that they are implicated with the disease.

'That so many of the mutations were found outside of protein-coding genes also underscores the need to sequence whole genomes to find all the mutations that occur in cancer,' said Dr Richard Wilson, co-author of the paper and director of Washington University’s Genome Centre. 'If we only look at genes with known or suspected links to cancer, we'll miss many mutations that are potentially relevant', he added.

Advances in sequencing technology mean speed and accuracy are rising whilst costs fall. Dr James Downing of St Jude Children's Research Hospital, writing in an accompanying editorial, emphasises this point: 'As these improvements continue, the cost of obtaining the complete DNA sequence of a cancer cell will rapidly decrease, thus making it possible to acquire data from a larger number of cancers'. The sequencing price for last week's publication totalled half a million dollars, taking just a few months to perform. This is one-third the price of sequencing the first cancer patient just ten months ago.

SOURCES & REFERENCES
New England Journal of Medicine | 05 August 2009
 
Science Daily | 06 August 2009
 
Cancer Research UK | 06 August 2009
 
Genome Web | 06 August 2009
 

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