454 Sequencing Systems and NimbleGen Sequence Capture Show Promise for Genetic Characterization of Leukemia
Leukemia is a cancer of the blood which causes rapid, abnormal proliferation of blood cells and consists of a broad spectrum of subtypes. While a number of treatment options are available, understanding the genetics and molecular composition of an individual's leukemia type is essential to determining the best course of action. Current methodologies are laborintensive, expensive, rely on expertknowledge, and often lack the sensitivity required to detect rare mutations. The MLL Munich Leukemia Laboratory team, led by Dr. Torsten Haferlach, CEO, recognized the power and speed of highthroughput sequencing to address these issues. "We identified 454 Sequencing technology as a promising method to characterize leukemia and other hematological malignancies. In our research on a variety of leukemia types and myeloproliferative neoplasms, we confirmed that not only are we able to comprehensively detect all types of known molecular mutations, but to identify also novel mutations, such as fusion partner genes resulting from balanced translocation events."
In one such study, the researchers used NimbleGen Sequence Capture 385K arrays to enrich a 1.91 Mb region of the genome containing 95 cancerassociated genes in 6 acute myeloid leukemia (AML) samples. They then sequenced the captured DNA with the GS FLX Titanium series chemistry and analyzed the results with the company's GS Reference Mapper software. The results showed, for the first time that point mutations, deletions and insertions, as well as fusion genes from translocations and inversions could be detected in a onestep methodological approach.
Another study presented by Dr. Alexander Kohlmann and Vera Grossmann used ultradeep sequencing of amplicons to accurately identify mutations in oncogenic regions within 95 samples of leukemia and myeloproliferative neoplasms. "Amplicon sequencing with the GS FLX System is a particularly straightforward and powerful method to detect a wide range of molecular mutations with high sensitivity. It is of particular utility for characterizing the constantly growing number of target genes used to distinguish molecular subtypes of hematological malignancies," explained Dr. Alexander Kohlmann, PhD, Head of the NGS group at the MLL. "This technology has the potential to immediately change the way we obtain novel molecular insights underlying this disease."
For more information on 454 Sequencing Systems, visit www.454.com. For more information on Roche Nimblegen Sequence Capture arrays, visit www.nimblegen.com.
Roche Diagnostics Deutschland GmbH
Headquartered in Basel, Switzerland, Roche is one of the world's leading researchfocused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in invitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2008 sales by the Pharmaceuticals Division totalled 36.0 billion Swiss francs, and the Diagnostics Division posted sales of 9.7 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested nearly 9 billion Swiss francs in R&D in 2008. Worldwide, the Group employs about 80,000 people. Additional information is available on the Internet at www.roche.com.
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