Genome Sequencer FLX System plus NimbleGen Sequence Capture Arrays Help Unravel the Cryptic Genetic Changes in Hematological Malignancies

The Cancer Genomics Group at Barts and The London Medical School is researching leukemia with the aquisition of the state-of-the-art Genome Sequencer FLX System paired with the Roche NimbleGen Sequence Capture arrays. Researchers, led by Professor Brian Young, will use the combined technology of 454 Sequencing and NimbleGen Sequence Capture Arrays to uncover the genetic changes that are involved in the development of leukemia. The new sequence information will be linked to an existing extensive clinical and cytogenetic database to investigate the relationship between genetic change and the clinical features of this devastating disease. The researchers expect that the new data could have implications for the future therapy and clinical outcome of hematological malignancies.

“454 Sequencing offers exciting new approaches to the investigation of cancer. Although many genes have been implicated in cancer, it is likely that there are many more that have yet to be discovered. The Cancer Genomics Group at Barts and The London Medical School is ideally placed to exploit this revolutionary technology. We wish to apply the massively parallel sequencing of 454 Sequencing to uncover all the genetic changes that initiate and drive the leukemia cells”, says Young, head of the Cancer Genomics Group.

Planned research projects include the sequence analysis of key genes and genomic regions that are involved in acute myeloid leukemia (AML), analysis of microRNA expression profiles and paired-end analysis of microdeletion events. More precisely, using the Roche NimbleGen Sequence Capture Arrays, the researchers plan to capture a series of genes involved in the development of the disease, including those known to be mutated in AML such as FLT3 and MLL, and characterize putative mutation targets through SNP genotype analysis. Analyzing full sequences of mutated genes (including introns) with the help of the Genome Sequencer FLX System the researchers strive to uncover the genetic variations that drive the initiation and development of leukemia.

The Cancer Genomics Group also plans to use the technology of 454 Sequencing to investigate the full pattern of microRNA expression in AML and compare it to known gene expression profiles for other leukemia subtypes. Analysis of these microRNA expression profiles is likely to help further unraveling the etiology of leukemia and may evolve into a tool for cancer classification. The researchers will also examine microdeletions, a type of genetic abnormality that appears to be a common characteristic feature of leukemias. Up to now, detection of microdeletions was limited by the availability of SNP markers. The unique technology of 454 Sequencing allows for a genome-wide analysis of microdeletions; its unbiased approach will increase the likelihood of finding all such events.