BRANFORD, Conn. - (Business Wire) 454 Life Sciences, a part of Roche Applied Science, today announced that researchers from The International Mesothelioma Program at Brigham and Women
’s Hospital and Harvard Medical School in Boston have used the 454 long-read sequencing technology to characterize for the first time mutations in expressed genes unique to malignant pleural mesotheliomas (MPMs). The 454 Sequencing system was used to comprehensively investigate the transcriptomes of 4 MPMs and two control tissues. The data revealed a number of genes which could be causally related to cancer including XRCC6, PDZK1IP1, ACTR1A, and AVEN. The study appeared today, in the Proceedings of the National Academy of Sciences.
Malignant pleural mesothelioma is a rapidly fatal cancer, whose genetic basis is unknown. In a majority of cases, MPM is related to previous exposure to asbestos. The aim of The International Mesothelioma Program is to understand the causative factors in the development of the disease and to translate their findings into improved therapy.
The study describes how researchers used Ultra-Deep 454 Sequencing to characterize the full compliment of individual tumor mutations in expressed genes in four MPM tumors and two controls. Between the four MPM samples, 15 tumor-specific, non-synonymous (protein altering) mutations were identified. These tumor-specific variations represent multiple types of mutations including somatic point mutations, RNA editing, Loss of Heterozygosity (LOH), and epigenetic silencing. Using the 454 Sequencing system, researchers detected single nucleotide variations with 96% sensitivity and 100% specificity. This body of work represents the first deep sequencing of the transcriptome of MPM tumor.
“Large scale sequencing of tumor transcriptomes may be useful for determining patient-specific mutational profiles, enabling discoveries that have the potential to impact individual patient care,” said Dr. David Sugarbaker, MD, lead author and Chief, Division of Thoracic Surgery at Brigham and Women’s Hospital, and founder of the International Mesothelioma Program. “We envision that this approach may ultimately form the basis of the molecular sub-typing of patients with cancer, allowing for therapy designed individually for each patient based on their mutational profile.”
Researchers chose a whole transcriptome based approach, where they used the Genome Sequencer System to sequence the messenger RNAs from expressed genes because this approach enriches for mutations in these genes, facilitating the identification of point mutations (variations in a single nucleotide), insertions and deletions, variant allele frequencies, haplotypes, and RNA editing. Furthermore, transcriptome sequencing with the Genome Sequencer System provides read-count based gene expression profiling.
"This study demonstrates the applicability of transcriptome sequencing with the Genome Sequencer System to the molecular characterization of heterogeneous tumor tissue," said Dr. Richard Gibbs, Ph.D. Wofford Cain Professor, Department of Molecular and Human Genetics and Director of the Human Genome Sequencing Center, Baylor College of Medicine. “The comprehensive identification of somatic mutations that potentially modify protein function is a key goal of The Cancer Genome Atlas that will lead to important advances in our fight to find more effective treatments, and ultimately, a cure for cancers."
“We are pleased to see the Genome Sequencer being used to improve our understanding of this devastating and complex disease,” said Christopher McLeod, president and CEO of 454 Life Sciences. “The Genome Sequencer System affords great advantage in the analysis of transcriptomes because of the long, high quality reads the system generates."
454 Life Sciences, a company of Roche Applied Science, develops and commercializes the innovative Genome Sequencer System for ultra-high-throughput DNA sequencing. Specific applications include de novo sequencing and re-sequencing of genomes, metagenomics, RNA analysis, and targeted sequencing of DNA regions of interest. The hallmarks of 454 Sequencing are its simple, unbiased sample preparation and long, highly accurate sequence reads, including paired reads. The technology used by 454 Sequencing has enabled many peer-reviewed studies in diverse research fields, such as cancer and infectious disease research, drug discovery, marine biology, anthropology, paleontology and many more.
For additional information, please visit http://www.454.com. For more information on the technology, visit www.roche-applied-science.com/sis/sequencing.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused 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 in-vitro 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 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available on the Internet at www.roche.com.
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454 Life Sciences
Brendon Hill, +1-(203)-871-2460
brendon.hill@roche.com
or
Roche Diagnostics GmbH
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