
DOI . ORG {
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Title[redir]:
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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Keywords {🔍}
mutations, multiple, myeloma, article, google, scholar, cas, nature, genes, cancer, supplementary, gene, patients, mutation, cell, fig, usa, regions, expression, cells, protein, sequencing, hoxa, data, braf, analysis, genome, table, role, observed, noncoding, pathogenesis, translation, point, ads, involved, nfκb, significant, rna, information, todd, somatic, set, clinical, previously, dis, human, center, including, pathway,
Topics {✒️}
nature portfolio privacy policy advertising pgc-1α-responsive genes involved social media library preparation lymphoma research early-stage mycosis fungoides reprints accession numbers gse26760 accession code gse26863 development illumina ga-ii sequencer multipurpose rna-decay machine 76-bp paired-end reads gene expression omnibus haematopoietic stem-cell stage40 cutaneous t-cell lymphomas46 hmt-related genomic events nature genet nature struct nature rev raf-erk signaling pathway noncanonical nf-κb pathway wgs libraries wes libraries published functional annotation mek/erk signalling cascade top-ranking gene set original author alternative nf-κb pathways reflect transcription-coupled repair braf-mutated multiple myeloma identified tumour-specific mutations silent protein-coding mutations massively parallel sequencing nature nature 465 nature 456 nature 461 nature 464 nature 463 nature 454 nature 417 nature 471 including rna/dna extraction mature b-lymphoid cells hoxa9-depleted cells exhibited permissions gfp-positive cells present
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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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Cancer genetics
Myeloma
Sequencing
Science
Humanities and Social Sciences
multidisciplinary
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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
pageStart:467
pageEnd:472
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keywords:
Cancer genetics
Myeloma
Sequencing
Science
Humanities and Social Sciences
multidisciplinary
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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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- How much does https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Michael%20A.%20Chapman earn?
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- https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Carrie%20Sougnez's total income per month
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- https://www.nature.com/articles/nature09837/search?author=Anna%20C.%20Schinzel's financial summary
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- How much money does https://www.nature.com/articles/nature09837/search?author=Yotam%20Drier generate?
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- What's the monthly money flow for https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Stacey%20B.%20Gabriel%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
- How much does https://www.nature.com/articles/nature09837/search?author=Craig%20C.%20Hofmeister generate monthly?
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- Revenue of https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Craig%20C.%20Hofmeister%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en
- What's the income of https://www.nature.com/articles/nature09837/search?author=Sundar%20Jagannath?
- Get to know what's the income of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Sundar%20Jagannath
- How much does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Sundar%20Jagannath%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en gross monthly?
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- Find out how much https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Andrzej%20J.%20Jakubowiak%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en earns monthly
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- Monthly income for https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Amrita%20Krishnan
- Learn how profitable https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Amrita%20Krishnan%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en is on a monthly basis
- What's the revenue for https://www.nature.com/articles/nature09837/search?author=Joan%20Levy?
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- Earnings of https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Ted%20Liefeld%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en
- What's the total monthly financial gain of https://www.nature.com/articles/nature09837/search?author=Sagar%20Lonial?
- Profit of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Sagar%20Lonial
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- How much revenue does https://www.nature.com/articles/nature09837/search?author=Scott%20Mahan bring in?
- Financial intake of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Scott%20Mahan
- How much revenue does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Scott%20Mahan%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en generate?
- Income figures for https://www.nature.com/articles/nature09837/search?author=Bunmi%20Mfuko
- Learn how profitable https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Bunmi%20Mfuko is on a monthly basis
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- What is the monthly revenue of https://www.nature.com/articles/nature09837/search?author=Stefano%20Monti?
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- How much income is https://www.nature.com/articles/nature09837/search?author=Louise%20M.%20Perkins earning monthly?
- What's the monthly income of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Louise%20M.%20Perkins?
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- Revenue of https://www.nature.com/articles/nature09837/search?author=A.%20Keith%20Stewart
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- What's the financial gain of https://www.nature.com/articles/nature09837/search?author=Suzanne%20Trudel?
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- Check the income stats for https://www.nature.com/articles/nature09837/search?author=Douglas%20Voet
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- Income figures for https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Jeff%20Trent
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