Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Mutations driving CLL and their evolution in progression and relapse.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
    • بيانات النشر:
      Publication: Basingstoke : Nature Publishing Group
      Original Publication: London, Macmillan Journals ltd.
    • الموضوع:
      Disease Progression* ; Evolution, Molecular*; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics ; Mutation/*genetics ; Neoplasm Recurrence, Local/*genetics; Cell Transformation, Neoplastic/genetics ; Clone Cells/metabolism ; Clone Cells/pathology ; DNA Copy Number Variations/genetics ; Exome/genetics ; Genes, myc/genetics ; Humans ; Ikaros Transcription Factor/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; MAP Kinase Signaling System/genetics ; Prognosis ; RNA Processing, Post-Transcriptional/genetics ; RNA Transport/genetics ; Ribosomal Proteins/genetics ; Treatment Outcome
    • نبذة مختصرة :
      Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
    • Comments:
      Comment in: Cell Death Dis. 2016;7:e2042. (PMID: 26775696)
    • References:
      Am J Hematol. 2015 May;90(5):446-60. (PMID: 25908509)
      Blood. 2012 Dec 6;120(24):4783-94. (PMID: 23047824)
      N Engl J Med. 2011 Jun 16;364(24):2305-15. (PMID: 21663470)
      Nat Genet. 2014 Feb;46(2):161-5. (PMID: 24413733)
      Cell. 2014 Oct 23;159(3):676-90. (PMID: 25417114)
      Oncogene. 2013 Jun 13;32(24):2907-16. (PMID: 22926519)
      Blood. 2011 Feb 10;117(6):1917-27. (PMID: 21139082)
      Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. (PMID: 24030381)
      Am J Hum Genet. 2008 Dec;83(6):769-80. (PMID: 19061985)
      Leuk Lymphoma. 2013 Jun;54(6):1177-82. (PMID: 23088640)
      Cancer Discov. 2014 Sep;4(9):1088-101. (PMID: 24920063)
      Nat Genet. 2013 Mar;45(3):229-31. (PMID: 23435090)
      Cell. 2013 Feb 14;152(4):714-26. (PMID: 23415222)
      Nature. 2014 Jan 23;505(7484):495-501. (PMID: 24390350)
      Blood. 2013 Feb 21;121(8):1403-12. (PMID: 23243274)
      Cell. 2013 Nov 7;155(4):948-62. (PMID: 24183448)
      Nature. 2011 Jul 7;475(7354):101-5. (PMID: 21642962)
      Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18545-50. (PMID: 20876136)
      Br J Haematol. 2009 Jan;144(2):268-70. (PMID: 19016725)
      Blood. 2014 May 22;123(21):3247-54. (PMID: 24652989)
      Nature. 2013 Jul 11;499(7457):214-8. (PMID: 23770567)
      Leuk Lymphoma. 2013 May;54(5):1087-90. (PMID: 23039309)
      Blood. 2013 Mar 7;121(10):1769-82. (PMID: 23303821)
      Genome Med. 2013 May 29;5(5):47. (PMID: 23731665)
      J Biol Chem. 2010 Oct 8;285(41):31895-906. (PMID: 20696760)
      Haematologica. 2014 Dec;99(12):1834-45. (PMID: 25193962)
      Haematologica. 2015 Jun;100(6):e237-9. (PMID: 25710457)
      Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16226-31. (PMID: 12446840)
      Oncogene. 2005 Jan 13;24(3):520-4. (PMID: 15516975)
      Nature. 2013 Aug 22;500(7463):415-21. (PMID: 23945592)
      Lancet. 2010 Oct 2;376(9747):1164-74. (PMID: 20888994)
      Mol Cell Biol. 2009 Jul;29(13):3687-99. (PMID: 19380490)
      Nat Genet. 2012 Jan;44(1):47-52. (PMID: 22158541)
      Cancer Res. 2010 Jul 1;70(13):5518-27. (PMID: 20551065)
      Elife. 2014;3. doi: 10.7554/eLife.02869. (PMID: 25496728)
      Science. 2013 Mar 29;339(6127):1546-58. (PMID: 23539594)
      Nat Biotechnol. 2012 May;30(5):413-21. (PMID: 22544022)
      Am J Pathol. 2002 Sep;161(3):957-68. (PMID: 12213724)
      Cell. 2010 Jan 22;140(2):209-21. (PMID: 20141835)
      Blood. 2012 Nov 15;120(20):4191-6. (PMID: 22915640)
    • Grant Information:
      U10 CA180861 United States CA NCI NIH HHS; 1U10CA180861-01 United States CA NCI NIH HHS; R01 CA182461 United States CA NCI NIH HHS; U54 HG003067 United States HG NHGRI NIH HHS; 1K01ES025431-01 United States ES NIEHS NIH HHS; 1R01CA182461-02 United States CA NCI NIH HHS; U54HG003067 United States HG NHGRI NIH HHS; K01 ES025431 United States ES NIEHS NIH HHS; P01 CA081534 United States CA NCI NIH HHS; 1R01CA184922-01 United States CA NCI NIH HHS; R01 CA184922 United States CA NCI NIH HHS; R01 HL116452 United States HL NHLBI NIH HHS
    • Molecular Sequence:
      dbGaP PHS000922.V1.P1
    • الرقم المعرف:
      0 (IKZF3 protein, human)
      0 (Ribosomal Proteins)
      0 (ribosomal protein S21)
      148971-36-2 (Ikaros Transcription Factor)
    • الموضوع:
      Date Created: 20151016 Date Completed: 20151117 Latest Revision: 20220317
    • الموضوع:
      20221213
    • الرقم المعرف:
      PMC4815041
    • الرقم المعرف:
      10.1038/nature15395
    • الرقم المعرف:
      26466571