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Title:
Initial genome sequencing and analysis of multiple myeloma | Nature
Description:
Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge. Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Chapman et al. have used next-generation sequencing to compare 38 multiple myeloma genomes with those of normal cells from the same patients. The disease involves mutations of genes with roles in protein translation, histone methylation and blood coagulation. In terms of clinically relevant findings, unexpected activating mutations were found in the kinase BRAF, inhibitors of which have recently shown dramatic clinical activity. This suggests that BRAF inhibitors should be evaluated in patients with BRAF-mutated multiple myeloma. Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.
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headline:Initial genome sequencing and analysis of multiple myeloma
description:Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge. Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Chapman et al. have used next-generation sequencing to compare 38 multiple myeloma genomes with those of normal cells from the same patients. The disease involves mutations of genes with roles in protein translation, histone methylation and blood coagulation. In terms of clinically relevant findings, unexpected activating mutations were found in the kinase BRAF, inhibitors of which have recently shown dramatic clinical activity. This suggests that BRAF inhibitors should be evaluated in patients with BRAF-mutated multiple myeloma. Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.
datePublished:2011-03-23T00:00:00Z
dateModified:2011-03-23T00:00:00Z
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ScholarlyArticle:
headline:Initial genome sequencing and analysis of multiple myeloma
description:Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge. Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Chapman et al. have used next-generation sequencing to compare 38 multiple myeloma genomes with those of normal cells from the same patients. The disease involves mutations of genes with roles in protein translation, histone methylation and blood coagulation. In terms of clinically relevant findings, unexpected activating mutations were found in the kinase BRAF, inhibitors of which have recently shown dramatic clinical activity. This suggests that BRAF inhibitors should be evaluated in patients with BRAF-mutated multiple myeloma. Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.
datePublished:2011-03-23T00:00:00Z
dateModified:2011-03-23T00:00:00Z
pageStart:467
pageEnd:472
license:http://creativecommons.org/licenses/by-nc-sa/3.0/
sameAs:https://doi.org/10.1038/nature09837
keywords:
Cancer genetics
Myeloma
Sequencing
Science
Humanities and Social Sciences
multidisciplinary
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name:Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Dana-Farber Cancer Institute, 44 Binney Street, Boston, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Massachusetts General Hospital, 55 Fruit Street, Boston, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Dana-Farber Cancer Institute, 44 Binney Street, Boston, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Multiple Myeloma Research Foundation, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, USA
name:Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Massachusetts General Hospital, 55 Fruit Street, Boston, USA
name:Harvard Medical School, Boston, USA
name:Howard Hughes Medical Institute, Chevy Chase, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel
name:Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Ohio State University Medical Center, 320 West 10th Avenue, Columbus, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:St Vincentâs Comprehensive Cancer Center, 325 West 15th Street, New York, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, Ann Arbor, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Multiple Myeloma Research Foundation, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Winship Cancer Institute, Emory University, 1365-C Clifton Road, NE Atlanta, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Multiple Myeloma Research Foundation, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Multiple Myeloma Research Foundation, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Mayo Clinic Rochester, 200 1st Street SW Rochester, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:John Theurer Cancer Center at Hackensack University Medical Center, 92 Second Street, Hackensack, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Princess Margaret Hospital, 610 University Avenue, Toronto, Canada
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:Washington University School of Medicine, Washington University in St Louis, St Louis, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor, Norwalk, USA
name:University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, USA
name:The Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, USA
name:The Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Dana-Farber Cancer Institute, 44 Binney Street, Boston, USA
name:Harvard Medical School, Boston, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Dana-Farber Cancer Institute, 44 Binney Street, Boston, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Dana-Farber Cancer Institute, 44 Binney Street, Boston, USA
name:Harvard Medical School, Boston, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Harvard Medical School, Boston, USA
name:Massachusetts Institute of Technology, Cambridge, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, USA
name:Dana-Farber Cancer Institute, 44 Binney Street, Boston, USA
name:Harvard Medical School, Boston, USA
name:Howard Hughes Medical Institute, Chevy Chase, USA
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