Page URL:

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

10 August 2009
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.

Cancer genomes - continuing progress
New England Journal of Medicine |  5 August 2009
Decoding Leukemia Patient Genome Leads Scientists To Mutations In Other Patients
Science Daily |  6 August 2009
Scientists sequence genome of second patient with AML
Cancer Research UK |  6 August 2009
WashU Team Publishes Second AML Genome
Genome Web |  6 August 2009
17 December 2012 - by Joseph Jebelli 
A seven-year-old girl with a highly aggressive form of leukaemia may have been 'cured' by an experimental therapy that harnesses the body's immune system to seek out and destroy the disease....
4 April 2011 - by Maren Urner 
Researchers from the Wellcome Trust Sanger Institute have identified three different genetic mutations linked to acute myeloid leukaemia (AML), a cancer that is characterised by a rapid increase in abnormal white blood cells in the bone marrow....
30 November 2009 - by Dr Rebecca Robey 
The link between a certain genetic mutation and the most common form of brain tumour has been unravelled by US scientists. The mutation, in a gene called IDH1, was already known to be associated with the development of brain cancers, but it was not known how the mutation contributed to the disease....
10 November 2008 - by Alison Cranage 
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...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.