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PMID: 20975063 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Clinical implications of the cancer genome.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology ·Vol. 28 ·No. 35 ·2010-12-10 ·Pages 5219-28

Macconaill LE, Garraway LA

Abstract

Cancer is a disease of the genome. Most tumors harbor a constellation of structural genomic alterations that may dictate their clinical behavior and treatment response. Whereas elucidating the nature and importance of these genomic alterations has been the goal of cancer biologists for several decades, ongoing global genome characterization efforts are revolutionizing both tumor biology and the optimal paradigm for cancer treatment at an unprecedented scope. The pace of advance has been empowered, in large part, through disruptive technological innovations that render complete cancer genome characterization feasible on a large scale. This article highlights cardinal biologic and clinical insights gleaned from systematic cancer genome characterization. We also discuss how the convergence of cancer genome biology, technology, and targeted therapeutics articulates a cohesive framework for the advent of personalized cancer medicine.

MeSH Terms
Animals Genome, Human Humans Neoplasms/genetics Precision Medicine/methods
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Macconaill Laura E
Center for Cancer Genome Discovery, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Garraway Levi A
References (86)
86 references, click to expand
  1. A comprehensive catalogue of somatic mutations from a human cancer genome.
    Nature. 2010 Jan 14;463(7278):191-6 PMID: 20016485
  2. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate.
    Cancer Cell. 2010 Mar 16;17(3):225-34 PMID: 20171147
  3. Mechanism of activation of a human oncogene.
    Nature. 1982 Nov 11;300(5888):143-9 PMID: 6290897
  4. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors.
    J Pharmacol Exp Ther. 2000 Oct;295(1):139-45 PMID: 10991971
  5. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene.
    Nature. 1982 Jun 10;297(5866):474-8 PMID: 6283357
  6. Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation.
    Pigment Cell Melanoma Res. 2008 Aug;21(4):492-3 PMID: 18510589
  7. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
    N Engl J Med. 2009 Sep 3;361(10):947-57 PMID: 19692680
  8. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line.
    Nature. 1982 Aug 12;298(5875):679-81 PMID: 6285209
  9. V599EB-RAF is an oncogene in melanocytes.
    Cancer Res. 2004 Apr 1;64(7):2338-42 PMID: 15059882
  10. Patterns of somatic mutation in human cancer genomes.
    Nature. 2007 Mar 8;446(7132):153-8 PMID: 17344846
  11. Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group.
    J Clin Oncol. 2008 May 1;26(13):2178-85 PMID: 18445842
  12. Integrating genetic approaches into the discovery of anticancer drugs.
    Science. 1997 Nov 7;278(5340):1064-8 PMID: 9353181
  13. Cancer. Addiction to oncogenes--the Achilles heal of cancer.
    Science. 2002 Jul 5;297(5578):63-4 PMID: 12098689
  14. Inhibition of mutated, activated BRAF in metastatic melanoma.
    N Engl J Med. 2010 Aug 26;363(9):809-19 PMID: 20818844
  15. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros.
    Nature. 2008 May 1;453(7191):110-4 PMID: 18408710
  16. Genome-wide in situ exon capture for selective resequencing.
    Nat Genet. 2007 Dec;39(12):1522-7 PMID: 17982454
  17. Association of amplified oncogene c-myc with an abnormally banded chromosome 8 in a human leukaemia cell line.
    Nature. 1983 Dec 1-7;306(5942):494-7 PMID: 6580529
  18. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining.
    Nature. 1973 Jun 1;243(5405):290-3 PMID: 4126434
  19. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA.
    Nature. 1976 Mar 11;260(5547):170-3 PMID: 176594
  20. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.
    N Engl J Med. 2009 Jul 9;361(2):123-34 PMID: 19553641
  21. An integrated genomic analysis of human glioblastoma multiforme.
    Science. 2008 Sep 26;321(5897):1807-12 PMID: 18772396
  22. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia.
    Nature. 1982 Dec 23;300(5894):765-7 PMID: 6960256
  23. Somatic activation of KIT in distinct subtypes of melanoma.
    J Clin Oncol. 2006 Sep 10;24(26):4340-6 PMID: 16908931
  24. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer.
    J Clin Oncol. 2009 Dec 10;27(35):5924-30 PMID: 19884556
  25. The consensus coding sequences of human breast and colorectal cancers.
    Science. 2006 Oct 13;314(5797):268-74 PMID: 16959974
  26. Rapid whole-genome mutational profiling using next-generation sequencing technologies.
    Genome Res. 2008 Oct;18(10):1638-42 PMID: 18775913
  27. Oncogene addiction.
    Cancer Res. 2008 May 1;68(9):3077-80; discussion 3080 PMID: 18451130
  28. Somatic mutations affect key pathways in lung adenocarcinoma.
    Nature. 2008 Oct 23;455(7216):1069-75 PMID: 18948947
  29. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.
    Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11 PMID: 15329413
  30. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.
    Nature. 2007 Apr 12;446(7137):758-64 PMID: 17344859
  31. Next-generation DNA sequencing.
    Nat Biotechnol. 2008 Oct;26(10):1135-45 PMID: 18846087
  32. Cellular uptake of the tyrosine kinase inhibitors imatinib and AMN107 in gastrointestinal stromal tumor cell lines.
    Pharmacology. 2006;77(1):11-6 PMID: 16534250
  33. Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer.
    Clin Cancer Res. 2005 Sep 15;11(18):6650-6 PMID: 16166444
  34. Chromosome studies on normal and leukemic human leukocytes.
    J Natl Cancer Inst. 1960 Jul;25:85-109 PMID: 14427847
  35. Modeling genomic diversity and tumor dependency in malignant melanoma.
    Cancer Res. 2008 Feb 1;68(3):664-73 PMID: 18245465
  36. High frequency of mutations of the PIK3CA gene in human cancers.
    Science. 2004 Apr 23;304(5670):554 PMID: 15016963
  37. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia.
    Blood. 1988 Aug;72(2):567-72 PMID: 3165295
  38. Mutations of the BRAF gene in human cancer.
    Nature. 2002 Jun 27;417(6892):949-54 PMID: 12068308
  39. Mutation and cancer: statistical study of retinoblastoma.
    Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3 PMID: 5279523
  40. The landscape of somatic copy-number alteration across human cancers.
    Nature. 2010 Feb 18;463(7283):899-905 PMID: 20164920
  41. High-throughput oncogene mutation profiling in human cancer.
    Nat Genet. 2007 Mar;39(3):347-51 PMID: 17293865
  42. Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris.
    J Cell Sci. 2008 Jan;121 Suppl 1:1-84 PMID: 18089652
  43. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing.
    Nat Biotechnol. 2009 Feb;27(2):182-9 PMID: 19182786
  44. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.
    J Clin Oncol. 2002 Feb 1;20(3):719-26 PMID: 11821453
  45. A small-cell lung cancer genome with complex signatures of tobacco exposure.
    Nature. 2010 Jan 14;463(7278):184-90 PMID: 20016488
  46. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells.
    Cell. 2009 May 29;137(5):821-34 PMID: 19490892
  47. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
    J Clin Oncol. 2007 Aug 1;25(22):3230-7 PMID: 17664471
  48. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1.
    Nature. 2009 Nov 5;462(7269):108-12 PMID: 19847166
  49. Genome sequencing in microfabricated high-density picolitre reactors.
    Nature. 2005 Sep 15;437(7057):376-80 PMID: 16056220
  50. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.
    Nat Genet. 2009 Nov;41(11):1238-42 PMID: 19801978
  51. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
    Science. 2004 Jun 4;304(5676):1497-500 PMID: 15118125
  52. Accurate whole human genome sequencing using reversible terminator chemistry.
    Nature. 2008 Nov 6;456(7218):53-9 PMID: 18987734
  53. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene.
    Cell. 2009 May 29;137(5):835-48 PMID: 19490893
  54. Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29.
    J Virol. 1982 Jun;42(3):773-9 PMID: 6284994
  55. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells.
    Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837-41 PMID: 6818551
  56. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity.
    Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6 PMID: 18287029
  57. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.
    J Clin Oncol. 2010 Jan 20;28(3):466-74 PMID: 20008640
  58. Profiling critical cancer gene mutations in clinical tumor samples.
    PLoS One. 2009 Nov 18;4(11):e7887 PMID: 19924296
  59. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour.
    Nature. 1983 Sep 15-21;305(5931):245-8 PMID: 6888561
  60. Recurring mutations found by sequencing an acute myeloid leukemia genome.
    N Engl J Med. 2009 Sep 10;361(11):1058-66 PMID: 19657110
  61. The concept of synthetic lethality in the context of anticancer therapy.
    Nat Rev Cancer. 2005 Sep;5(9):689-98 PMID: 16110319
  62. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707-11 PMID: 6300869
  63. PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer.
    J Clin Oncol. 2009 Mar 20;27(9):1477-84 PMID: 19237633
  64. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
    Nature. 2007 Aug 2;448(7153):561-6 PMID: 17625570
  65. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays.
    Science. 2010 Jan 1;327(5961):78-81 PMID: 19892942
  66. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer.
    Nature. 2007 Aug 2;448(7153):595-9 PMID: 17671502
  67. Comprehensive genomic characterization defines human glioblastoma genes and core pathways.
    Nature. 2008 Oct 23;455(7216):1061-8 PMID: 18772890
  68. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
    Nature. 2008 Nov 6;456(7218):66-72 PMID: 18987736
  69. Characterizing the cancer genome in lung adenocarcinoma.
    Nature. 2007 Dec 6;450(7171):893-8 PMID: 17982442
  70. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.
    Nature. 2005 Jul 7;436(7047):117-22 PMID: 16001072
  71. Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine.
    EMBO Mol Med. 2010 May;2(5):146-58 PMID: 20432502
  72. Major response to imatinib mesylate in KIT-mutated melanoma.
    J Clin Oncol. 2008 Apr 20;26(12):2046-51 PMID: 18421059
  73. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.
    J Clin Oncol. 2008 Jan 20;26(3):374-9 PMID: 18202412
  74. Amplification and expression of the c-myc oncogene in human lung cancer cell lines.
    Nature. 1983 Nov 10-16;306(5939):194-6 PMID: 6646201
  75. Comment on "The consensus coding sequences of human breast and colorectal cancers".
    Science. 2007 Sep 14;317(5844):1500 PMID: 17872428
  76. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.
    Science. 2005 Oct 28;310(5748):644-8 PMID: 16254181
  77. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results.
    Blood. 1990 Nov 1;76(9):1704-9 PMID: 2224119
  78. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
    N Engl J Med. 2004 May 20;350(21):2129-39 PMID: 15118073
  79. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.
    N Engl J Med. 2009 Jan 29;360(5):470-80 PMID: 19129520
  80. Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer.
    J Clin Oncol. 2004 Nov 15;22(22):4456-62 PMID: 15483017
  81. Cancer epigenomics: DNA methylomes and histone-modification maps.
    Nat Rev Genet. 2007 Apr;8(4):286-98 PMID: 17339880
  82. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution.
    Nature. 2009 Oct 8;461(7265):809-13 PMID: 19812674
  83. Accurate multiplex polony sequencing of an evolved bacterial genome.
    Science. 2005 Sep 9;309(5741):1728-32 PMID: 16081699
  84. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
    N Engl J Med. 2002 Aug 15;347(7):472-80 PMID: 12181401
  85. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma.
    Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20007-12 PMID: 18077431
  86. The genomic landscapes of human breast and colorectal cancers.
    Science. 2007 Nov 16;318(5853):1108-13 PMID: 17932254
Article Info
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Abbr.
J Clin Oncol
ISSN
1527-7755
DOI
10.1200/JCO.2009.27.4944
Published
2010-12-10
Epub
2010-00-25
Pages
5219-28
Language
English
Region
United States
NLM ID
8309333
PMCID
PMC3020694
Subset
IM
Grants
NCI NIH HHS · R21 CA126674 · United States
NCI NIH HHS · R21CA126674 · United States
External Links
PubMed source DOI: 10.1200/JCO.2009.27.4944 PMC Full Text View journal details
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