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PMID: 19081671 Published · ppublish English Journal Article Review

Cancer driver mutations in protein kinase genes.

Cancer letters ·Vol. 281 ·No. 2 ·2009-08-28 ·Pages 117-27

Torkamani A, Verkhivker G, Schork NJ

Abstract

Recent studies investigating the genetic determinants of cancer suggest that some of the genetic alterations contributing to tumorigenesis may be inherited, but the vast majority is somatically acquired during the transition of a normal cell to a cancer cell. A systematic understanding of the genetic and molecular determinants of cancers has already begun to have a transformative effect on the study and treatment of cancer, particularly through the identification of a range of genetic alterations in protein kinase genes, which are highly associated with the disease. Since kinases are prominent therapeutic targets for intervention within the cancer cell, studying the impact that genomic alterations within them have on cancer initiation, progression, and treatment is both logical and timely. In fact, recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for protein kinase 'driver' mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to kinase 'passenger' mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation. In this review, we discuss the recent progress in the discovery and functional characterization of protein kinase cancer driver mutations and the implications of this progress for understanding tumorigenesis as well as the design of 'personalized' cancer therapeutics that target an individual's unique mutational profile.

MeSH Terms
Animals Cell Transformation, Neoplastic/genetics Humans Mutation Neoplasms/enzymology,genetics Protein Kinases/genetics
Chemicals
Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Torkamani Ali
The Scripps Translational Science Institute and Scripps Genomic Medicine, Scripps Health and The Scripps Research Institute, La Jolla, CA 92037, USA.
Verkhivker Gennady
Schork Nicholas J
References (132)
132 references, click to expand
  1. The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer.
    Hum Mutat. 2006 Jun;27(6):538-44 PMID: 16652348
  2. Structural evolution of the protein kinase-like superfamily.
    PLoS Comput Biol. 2005 Oct;1(5):e49 PMID: 16244704
  3. Somatic mutations of the protein kinase gene family in human lung cancer.
    Cancer Res. 2005 Sep 1;65(17):7591-5 PMID: 16140923
  4. K252a inhibits the oncogenic properties of Met, the HGF receptor.
    Oncogene. 2002 Jul 25;21(32):4885-93 PMID: 12118367
  5. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP.
    Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5 PMID: 18227510
  6. Oncogenomics and the development of new cancer therapies.
    Nature. 2004 May 27;429(6990):469-74 PMID: 15164073
  7. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
    FASEB J. 1995 May;9(8):576-96 PMID: 7768349
  8. A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.
    J Biol Chem. 2004 Dec 31;279(53):55827-32 PMID: 15507431
  9. Patterns of somatic mutation in human cancer genomes.
    Nature. 2007 Mar 8;446(7132):153-8 PMID: 17344846
  10. The protein kinase complement of the human genome.
    Science. 2002 Dec 6;298(5600):1912-34 PMID: 12471243
  11. EGFR somatic doublets in lung cancer are frequent and generally arise from a pair of driver mutations uncommonly seen as singlet mutations: one-third of doublets occur at five pairs of amino acids.
    Oncogene. 2008 Jul 17;27(31):4336-43 PMID: 18372921
  12. The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation.
    Structure. 2005 Jun;13(6):861-71 PMID: 15939018
  13. Cancer. Addiction to oncogenes--the Achilles heal of cancer.
    Science. 2002 Jul 5;297(5578):63-4 PMID: 12098689
  14. Crystal structure of the T315I Abl mutant in complex with the aurora kinases inhibitor PHA-739358.
    Cancer Res. 2007 Sep 1;67(17):7987-90 PMID: 17804707
  15. CHEK2 is a multiorgan cancer susceptibility gene.
    Am J Hum Genet. 2004 Dec;75(6):1131-5 PMID: 15492928
  16. Structural and functional diversity of the microbial kinome.
    PLoS Biol. 2007 Mar;5(3):e17 PMID: 17355172
  17. c-Met inhibitors with different binding modes: two is better than one.
    Cell Cycle. 2008 May 1;7(9):1157-60 PMID: 18418040
  18. A census of human cancer genes.
    Nat Rev Cancer. 2004 Mar;4(3):177-83 PMID: 14993899
  19. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
    J Biol Chem. 2004 Jul 23;279(30):31655-63 PMID: 15123710
  20. The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272.
    Oncogene. 2007 Jul 26;26(34):5023-7 PMID: 17311002
  21. Distinguishing cancer-associated missense mutations from common polymorphisms.
    Cancer Res. 2007 Jan 15;67(2):465-73 PMID: 17234753
  22. Genomics. Billion-dollar cancer mapping project steps forward.
    Science. 2008 Jul 4;321(5885):26-7 PMID: 18599748
  23. The role of companion diagnostics in the development and use of mutation-targeted cancer therapies.
    Nat Biotechnol. 2006 Aug;24(8):985-95 PMID: 16900147
  24. In silico profiling of tyrosine kinases binding specificity and drug resistance using Monte Carlo simulations with the ensembles of protein kinase crystal structures.
    Biopolymers. 2007 Mar;85(4):333-48 PMID: 17167796
  25. Human Cancer Genome Project moving forward despite some doubts in community.
    J Natl Cancer Inst. 2005 Sep 21;97(18):1322-4 PMID: 16174849
  26. Prediction of cancer driver mutations in protein kinases.
    Cancer Res. 2008 Mar 15;68(6):1675-82 PMID: 18339846
  27. KinMutBase: a registry of disease-causing mutations in protein kinase domains.
    Hum Mutat. 2005 May;25(5):435-42 PMID: 15832311
  28. Imprint of evolutionary conservation and protein structure variation on the binding function of protein tyrosine kinases.
    Bioinformatics. 2006 Aug 1;22(15):1846-54 PMID: 16720585
  29. Crystal structure of the T315I mutant of AbI kinase.
    Chem Biol Drug Des. 2007 Sep;70(3):171-81 PMID: 17718712
  30. The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants.
    Oncogene. 2004 Jul 8;23(31):5387-93 PMID: 15064724
  31. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants.
    PLoS Med. 2005 Nov;2(11):e313 PMID: 16187797
  32. The development of imatinib as a therapeutic agent for chronic myeloid leukemia.
    Blood. 2005 Apr 1;105(7):2640-53 PMID: 15618470
  33. Structural basis of oncogenic activation caused by point mutations in the kinase domain of the MET proto-oncogene: modeling studies.
    Proteins. 2001 Jul 1;44(1):32-43 PMID: 11354004
  34. Genomics: journey to the center of biology.
    Science. 2000 Mar 10;287(5459):1777-82 PMID: 10755930
  35. 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
  36. The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants.
    Cancer Res. 2006 Jun 1;66(11):5790-7 PMID: 16740718
  37. Exploring sequence-structure relationships in the tyrosine kinome space: functional classification of the binding specificity mechanisms for cancer therapeutics.
    Bioinformatics. 2007 Aug 1;23(15):1919-26 PMID: 17537753
  38. Features of selective kinase inhibitors.
    Chem Biol. 2005 Jun;12(6):621-37 PMID: 15975507
  39. Sensitive detection of KIT D816V in patients with mastocytosis.
    Clin Chem. 2006 Dec;52(12):2250-7 PMID: 17040960
  40. Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B.
    Cancer Res. 2006 Nov 15;66(22):10741-9 PMID: 17108110
  41. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.
    Cancer Res. 2004 Sep 15;64(18):6652-9 PMID: 15374980
  42. Congenital disease SNPs target lineage specific structural elements in protein kinases.
    Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9011-6 PMID: 18579784
  43. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor.
    Cell. 2006 Jun 16;125(6):1137-49 PMID: 16777603
  44. Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia.
    Blood. 2008 May 1;111(9):4797-808 PMID: 18270328
  45. Tumorigenesis mediated by MET mutant M1268T is inhibited by dominant-negative Src.
    Oncogene. 2000 Jun 15;19(26):2996-3002 PMID: 10871851
  46. The RAF proteins take centre stage.
    Nat Rev Mol Cell Biol. 2004 Nov;5(11):875-85 PMID: 15520807
  47. Mutations in the met oncogene unveil a "dual switch" mechanism controlling tyrosine kinase activity.
    J Biol Chem. 2003 Aug 1;278(31):29352-8 PMID: 12746450
  48. The genesis of high-throughput structure-based drug discovery using protein crystallography.
    Curr Opin Chem Biol. 2002 Oct;6(5):704-10 PMID: 12413557
  49. Modelling the molecular circuitry of cancer.
    Nat Rev Cancer. 2002 May;2(5):331-41 PMID: 12044009
  50. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.
    Blood. 2001 Apr 15;97(8):2434-9 PMID: 11290608
  51. The consensus coding sequences of human breast and colorectal cancers.
    Science. 2006 Oct 13;314(5797):268-74 PMID: 16959974
  52. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
    Science. 1991 Jul 26;253(5018):407-14 PMID: 1862342
  53. Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680.
    Cancer Lett. 2007 Jun 28;251(2):323-9 PMID: 17240048
  54. Structure and chemical inhibition of the RET tyrosine kinase domain.
    J Biol Chem. 2006 Nov 3;281(44):33577-87 PMID: 16928683
  55. 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
  56. Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma.
    Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5372-7 PMID: 12697903
  57. A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
    Science. 1995 Jun 23;268(5218):1749-53 PMID: 7792600
  58. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain.
    Mol Cell. 2004 Jan 30;13(2):169-78 PMID: 14759363
  59. Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles.
    Cancer Cell. 2007 Dec;12(6):501-13 PMID: 18068628
  60. Mechanisms of disease: Oncogene addiction--a rationale for molecular targeting in cancer therapy.
    Nat Clin Pract Oncol. 2006 Aug;3(8):448-57 PMID: 16894390
  61. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12654-9 PMID: 14559966
  62. Computational proteomics of biomolecular interactions in the sequence and structure space of the tyrosine kinome: deciphering the molecular basis of the kinase inhibitors selectivity.
    Proteins. 2007 Mar 1;66(4):912-29 PMID: 17173284
  63. Chromosome studies on normal and leukemic human leukocytes.
    J Natl Cancer Inst. 1960 Jul;25:85-109 PMID: 14427847
  64. Mutation profiling of mismatch repair-deficient colorectal cncers using an in silico genome scan to identify coding microsatellites.
    Cancer Res. 2002 Mar 1;62(5):1284-8 PMID: 11888892
  65. Somatic mutations in the DNA damage-response genes ATR and CHK1 in sporadic stomach tumors with microsatellite instability.
    Cancer Res. 2001 Nov 1;61(21):7727-30 PMID: 11691784
  66. High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia.
    Blood. 2008 May 1;111(9):4788-96 PMID: 18252861
  67. Two mutations affecting conserved residues in the Met receptor operate via different mechanisms.
    Oncogene. 2000 Mar 2;19(10):1354-61 PMID: 10713677
  68. High frequency of mutations of the PIK3CA gene in human cancers.
    Science. 2004 Apr 23;304(5670):554 PMID: 15016963
  69. Mutations of the BRAF gene in human cancer.
    Nature. 2002 Jun 27;417(6892):949-54 PMID: 12068308
  70. Comment on "The consensus coding sequences of human breast and colorectal cancers".
    Science. 2007 Sep 14;317(5844):1500; author reply 1500 PMID: 17872427
  71. c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty.
    Structure. 2007 Mar;15(3):299-311 PMID: 17355866
  72. CanPredict: a computational tool for predicting cancer-associated missense mutations.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W595-8 PMID: 17537827
  73. Accurate prediction of deleterious protein kinase polymorphisms.
    Bioinformatics. 2007 Nov 1;23(21):2918-25 PMID: 17855419
  74. High-throughput oncogene mutation profiling in human cancer.
    Nat Genet. 2007 Mar;39(3):347-51 PMID: 17293865
  75. Mutational analysis of the tyrosine phosphatome in colorectal cancers.
    Science. 2004 May 21;304(5674):1164-6 PMID: 15155950
  76. Signaling--2000 and beyond.
    Cell. 2000 Jan 7;100(1):113-27 PMID: 10647936
  77. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib.
    N Engl J Med. 2005 Feb 24;352(8):786-92 PMID: 15728811
  78. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib.
    Cancer Res. 2007 Dec 15;67(24):11924-32 PMID: 18089823
  79. Oncogene addiction: setting the stage for molecularly targeted cancer therapy.
    Genes Dev. 2007 Dec 15;21(24):3214-31 PMID: 18079171
  80. A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer.
    Nat Genet. 2005 Jun;37(6):590-2 PMID: 15908952
  81. Constitutively active mutant D816VKit induces megakayocyte and mast cell differentiation of early haemopoietic cells from murine foetal liver.
    Leuk Res. 2003 Jun;27(6):547-55 PMID: 12648515
  82. Lessons learned from the development of imatinib.
    Leuk Res. 2004 May;28 Suppl 1:S29-38 PMID: 15036939
  83. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
    Science. 2004 Jun 4;304(5676):1497-500 PMID: 15118125
  84. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.
    N Engl J Med. 2001 Apr 5;344(14):1038-42 PMID: 11287973
  85. RET signaling in endocrine tumors: delving deeper into molecular mechanisms.
    Endocr Pathol. 2007 Summer;18(2):57-67 PMID: 17916994
  86. The conformational plasticity of protein kinases.
    Cell. 2002 May 3;109(3):275-82 PMID: 12015977
  87. Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase.
    Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3563-8 PMID: 16537444
  88. c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations.
    J Biol Chem. 2008 Feb 1;283(5):2675-83 PMID: 18055465
  89. High-throughput mutational screen of the tyrosine kinome in chronic myelomonocytic leukemia.
    Leukemia. 2009 Feb;23(2):406-9 PMID: 18615102
  90. RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2B.
    Cancer Res. 2006 Oct 15;66(20):10179-87 PMID: 17047083
  91. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.
    Cell. 2004 Mar 19;116(6):855-67 PMID: 15035987
  92. Regulation of protein kinases; controlling activity through activation segment conformation.
    Mol Cell. 2004 Sep 10;15(5):661-75 PMID: 15350212
  93. Predicting deleterious amino acid substitutions.
    Genome Res. 2001 May;11(5):863-74 PMID: 11337480
  94. Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategies.
    Leukemia. 2003 Jul;17(7):1211-62 PMID: 12835715
  95. Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion.
    Cancer Res. 2002 Dec 1;62(23):7025-30 PMID: 12460923
  96. A second generation human haplotype map of over 3.1 million SNPs.
    Nature. 2007 Oct 18;449(7164):851-61 PMID: 17943122
  97. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
    J Biol Chem. 2002 Nov 29;277(48):46265-72 PMID: 12196540
  98. Cancer: drivers and passengers.
    Nature. 2007 Mar 8;446(7132):145-6 PMID: 17344839
  99. The protein kinases of budding yeast: six score and more.
    Trends Biochem Sci. 1997 Jan;22(1):18-22 PMID: 9020587
  100. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy.
    Cancer Res. 2006 Apr 15;66(8):3987-91 PMID: 16618716
  101. Imatinib mesylate in the treatment of chronic myeloid leukaemia.
    Expert Opin Pharmacother. 2003 Jun;4(6):963-71 PMID: 12783592
  102. Lung cancer: intragenic ERBB2 kinase mutations in tumours.
    Nature. 2004 Sep 30;431(7008):525-6 PMID: 15457249
  103. Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia.
    Br J Haematol. 2001 Jun;113(4):983-8 PMID: 11442493
  104. Structure and clinical relevance of the epidermal growth factor receptor in human cancer.
    J Clin Oncol. 2008 Apr 1;26(10):1742-51 PMID: 18375904
  105. Comment on "The consensus coding sequences of human breast and colorectal cancers".
    Science. 2007 Sep 14;317(5844):1500 PMID: 17872429
  106. Molecular implications of RET mutations for pheochromocytoma risk in multiple endocrine neoplasia 2.
    Ann N Y Acad Sci. 2006 Aug;1073:234-40 PMID: 17102091
  107. Sorafenib functions to potently suppress RET tyrosine kinase activity by direct enzymatic inhibition and promoting RET lysosomal degradation independent of proteasomal targeting.
    J Biol Chem. 2007 Oct 5;282(40):29230-40 PMID: 17664273
  108. Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase.
    J Med Chem. 2008 May 22;51(10):2879-82 PMID: 18426196
  109. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  110. Structural framework for the protein kinase family.
    Annu Rev Cell Biol. 1992;8:429-62 PMID: 1335745
  111. Specific targeted therapy of chronic myelogenous leukemia with imatinib.
    Pharmacol Rev. 2003 Sep;55(3):401-23 PMID: 12869662
  112. Imatinib as a paradigm of targeted therapies.
    Adv Cancer Res. 2004;91:1-30 PMID: 15327887
  113. Active and inactive protein kinases: structural basis for regulation.
    Cell. 1996 Apr 19;85(2):149-58 PMID: 8612268
  114. Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts.
    Cancer Res. 1998 Jul 1;58(13):2825-31 PMID: 9661897
  115. Mapping the cancer genome. Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies.
    Sci Am. 2007 Mar;296(3):50-7 PMID: 17348159
  116. Comment on "The consensus coding sequences of human breast and colorectal cancers".
    Science. 2007 Sep 14;317(5844):1500 PMID: 17872428
  117. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults.
    Genes Chromosomes Cancer. 2006 Jan;45(1):42-6 PMID: 16175573
  118. Protein kinases as therapeutic targets.
    Pharm Res. 2000 Nov;17(11):1345-53 PMID: 11205726
  119. 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
  120. Evolution of protein kinase signaling from yeast to man.
    Trends Biochem Sci. 2002 Oct;27(10):514-20 PMID: 12368087
  121. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.
    Cancer Cell. 2007 Mar;11(3):217-27 PMID: 17349580
  122. Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
    Science. 1991 Jul 26;253(5018):414-20 PMID: 1862343
  123. Approaches to comparative sequence analysis: towards a functional view of vertebrate genomes.
    Nat Rev Genet. 2008 Apr;9(4):303-13 PMID: 18347593
  124. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.
    N Engl J Med. 2001 Apr 5;344(14):1031-7 PMID: 11287972
  125. Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680.
    Cancer Res. 2006 Jan 15;66(2):1007-14 PMID: 16424036
  126. A Src-like inactive conformation in the abl tyrosine kinase domain.
    PLoS Biol. 2006 May;4(5):e144 PMID: 16640460
  127. Mutational analysis of the tyrosine kinome in colorectal cancers.
    Science. 2003 May 9;300(5621):949 PMID: 12738854
  128. Mutually exclusive NRASQ61R and BRAFV600E mutations at the single-cell level in the same human melanoma.
    Oncogene. 2006 Jun 8;25(24):3357-64 PMID: 16462768
  129. Novel oncogenic protein kinase inhibitors for cancer therapy.
    Curr Med Chem Anticancer Agents. 2004 Sep;4(5):449-55 PMID: 15379702
  130. The genomic landscapes of human breast and colorectal cancers.
    Science. 2007 Nov 16;318(5853):1108-13 PMID: 17932254
  131. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas.
    Oncogene. 2000 Mar 16;19(12):1547-55 PMID: 10734314
  132. The BCR-ABL story: bench to bedside and back.
    Annu Rev Immunol. 2004;22:247-306 PMID: 15032571
Article Info
Journal
Cancer letters
Abbr.
Cancer Lett
ISSN
1872-7980
DOI
10.1016/j.canlet.2008.11.008
Published
2009-08-28
Epub
2008-00-10
Pages
117-27
Language
English
Region
Ireland
NLM ID
7600053
PMCID
PMC2905872
Subset
IM
Grants
NCRR NIH HHS · UL1 RR025774 · United States
NCRR NIH HHS · UL1 RR025774-02 · United States
External Links
PubMed source DOI: 10.1016/j.canlet.2008.11.008 PMC Full Text View journal details
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