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Method improved for finding genetic mistakes

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A computer tool for finding the genetic missteps that fuel cancer has been developed by US researchers working on children's cancers. At the beginning of 2010, St Jude Children’s Research Hospital in Memphis, Tennessee, and Washington University School of Medicine in St Louis, Missouri,  embarked on a research programme to identify the genetic changes that give rise to some of the world’s deadliest childhood cancers. The teams joined forces to decode the genomes of more than 600 patients with childhood cancer, who contributed tumour samples.  

The researchers are now using the new algorithm to help identify the chromosomal rearrangements and DNA insertions or deletions unique to cancer. The new computational method known as CREST (Clipping Reveals Structure) enabled the identification of 89 new structural differences in the cancer genomes of five St Jude patients with a subtype of acute lymphoblastic leukaemia (ALL) known as T-lineage ALL. CREST revealed complex chromosomal rearrangements, including one that involved four chromosomes. Investigators also used the tool to find 50 new variations in melanoma cells. The study appears in the 12 June advance online edition of scientific journal Nature Methods.

‘CREST is significantly more accurate and sensitive than existing methods of finding structural variations in next-generation sequencing data. It finds differences between a patient’s normal and cancer genomes other tools cannot find,’ said Jinghui Zhang, an associate member of the St Jude Department of Computational Biology. She is the study’s senior author. ‘Similar tools miss up to 60 to 70 per cent of these structural rearrangements in tumours. CREST ensures that scientists will be able to find important structural variations that play critical roles in tumour formation.’