title: Detecting and targetting oncogenic fusion proteins in the genomic era.
abstract: The advent of widespread cancer genome sequencing has accelerated our understanding of the molecular aberrations underlying malignant disease at an unprecedented rate. Coupling the large number of bioinformatic methods developed to locate genomic breakpoints with increased sequence read length and a deeper understanding of coding region function has enabled rapid identification of novel actionable oncogenic fusion genes. Using examples of kinase fusions found in liquid and solid tumours, this review highlights major concepts that have arisen in our understanding of cancer pathogenesis through the study of fusion proteins. We provide an overview of recently developed methods to identify potential fusion proteins from next-generation sequencing data, describe the validation of their oncogenic potential and discuss the role of targetted therapies in treating cancers driven by fusion oncoproteins.
authors: Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, U.S.A; Department of Pediatrics, Oregon Health & Science University, Portland, OR, 97239, U.S.A.
authors: Monika A
authors: MA
authors: Davare
authors: Cristina E
authors: CE
authors: Tognon
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion
keywords: Cancer; Oncology/cancer; Other receptors; Protein kinases/phosphatases; Targeted therapy
references: Nat Genet. 2013 Aug;45(8):927-32
references: 23817572
references: Bioinformatics. 2012 Jun 15;28(12):i179-87
references: 22689759
references: Diagn Pathol. 2011 Mar 15;6:19
references: 21401966
references: Bioinformatics. 2012 Apr 1;28(7):1024-5
references: 22302574
references: Proc Natl Acad Sci U S A. 1987 Dec;84(24):9270-4
references: 2827175
references: Annu Rev Neurosci. 2001;24:677-736
references: 11520916
references: Clin Cancer Res. 2009 Oct 1;15(19):5962-7
references: 19755385
references: Lab Invest. 2003 Sep;83(9):1255-65
references: 13679433
references: Bioinformatics. 2011 Jun 1;27(11):1481-8
references: 21478487
references: Nucleic Acids Res. 2012 Sep;40(16):e123
references: 22570408
references: Cancer Lett. 2001 Aug 28;169(2):107-14
references: 11431098
references: PLoS One. 2012;7(2):e31323
references: 22347464
references: Mol Oncol. 2014 Dec;8(8):1495-507
references: 24962792
references: Cell. 2007 Dec 14;131(6):1190-203
references: 18083107
references: Genes Chromosomes Cancer. 2003 May;37(1):58-71
references: 12661006
references: Am J Surg Pathol. 2011 Oct;35(10):1600-2
references: 21934478
references: Cancer Cell. 2014 Apr 14;25(4):530-42
references: 24735925
references: Cancer Cell. 2014 Sep 8;26(3):428-442
references: 25132497
references: Oncogene. 2014 Oct 30;33(44):5183-92
references: 24186205
references: PLoS One. 2011;6(12):e28250
references: 22163003
references: Clin Cancer Res. 2013 Aug 1;19(15):4040-5
references: 23719267
references: Science. 1994 Mar 4;263(5151):1281-4
references: 8122112
references: Bioinformatics. 2011 Jun 15;27(12):1708-10
references: 21546395
references: Clin Cancer Res. 2014 Nov 15;20(22):5686-96
references: 25228534
references: N Engl J Med. 2014 Dec 4;371(23):2167-77
references: 25470694
references: Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):87-92
references: 23131561
references: Blood. 1999 Nov 1;94(9):3265-8
references: 10556217
references: Am J Pathol. 1998 Nov;153(5):1451-8
references: 9811336
references: Nat Med. 2012 Feb 12;18(3):378-81
references: 22327623
references: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):916-21
references: 12538861
references: Blood. 2007 Oct 1;110(7):2242-9
references: 17496200
references: Genome Res. 2012 Nov;22(11):2250-61
references: 22745232
references: Bioinformatics. 2011 Oct 15;27(20):2903-4
references: 21840877
references: Nat Med. 2013 Nov;19(11):1469-1472
references: 24162815
references: Clin Cancer Res. 2012 Dec 15;18(24):6599-608
references: 23052255
references: Nihon Rinsho. 1992 Jun;50(6):1363-8
references: 1325570
references: Genomics. 1993 Nov;18(2):397-400
references: 8288244
references: Sci Transl Med. 2012 Feb 8;4(120):120ps2
references: 22323827
references: Cell. 2000 Jan 7;100(1):57-70
references: 10647931
references: Cancer Cell. 2002 Nov;2(5):367-76
references: 12450792
references: PLoS One. 2014 Jan 27;9(1):e87170
references: 24475247
references: Cancer Discov. 2013 Jun;3(6):630-5
references: 23533264
references: Nucleic Acids Res. 2011 Aug;39(15):e100
references: 21622959
references: J Mol Diagn. 2014 May;16(3):361-70
references: 24517889
references: Cancer Res. 2012 Jul 1;72(13):3312-23
references: 22570254
references: Mol Cancer Ther. 2011 Apr;10(4):569-79
references: 21474455
references: Oncologist. 2014 Mar;19(3):235-42
references: 24563076
references: Genome Biol. 2011 Aug 11;12(8):R72
references: 21835007
references: Nat Med. 2009 Oct;15(10):1149-52
references: 19812576
references: Am J Pathol. 2000 Aug;157(2):377-84
references: 10934142
references: N Engl J Med. 2013 Jun 20;368(25):2395-401
references: 23724914
references: Nat Rev Clin Oncol. 2014 Aug;11(8):473-81
references: 24981256
references: Mol Cell Biol. 2006 Mar;26(5):1754-69
references: 16478996
references: Clin Cancer Res. 2008 Jun 1;14(11):3395-400
references: 18519769
references: Brief Bioinform. 2013 Jul;14(4):506-19
references: 22877769
references: Cancer. 2012 Jan 15;118(2):293-9
references: 21732333
references: Target Oncol. 2013 Mar;8(1):55-67
references: 23325296
references: BMC Syst Biol. 2014 Sep 04;8:97
references: 25183062
references: PLoS Comput Biol. 2011 May;7(5):e1001138
references: 21625565
references: Clin Lymphoma Myeloma. 2007 Mar;7 Suppl 3:S120-30
references: 17382021
references: Curr Opin Investig Drugs. 2010 Dec;11(12):1477-90
references: 21154129
references: Cancer Res. 1998 Nov 15;58(22):5046-8
references: 9823307
references: Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19519-24
references: 24218589
references: Cancer Cell. 2007 Dec;12(6):542-58
references: 18068631
references: Clin Cancer Res. 2012 Mar 1;18(5):1472-82
references: 22235099
references: Leukemia. 2000 Sep;14(9):1533-59
references: 10994999
references: Am J Pathol. 2001 Aug;159(2):411-5
references: 11485898
references: Mol Cancer Res. 2009 Sep;7(9):1466-76
references: 19737969
references: BMC Genomics. 2013 Nov 22;14:818
references: 24261984
references: Am J Pathol. 2000 Mar;156(3):781-9
references: 10702393
references: Nat Genet. 1998 Feb;18(2):184-7
references: 9462753
references: Clin Cancer Res. 2008 Oct 15;14(20):6618-24
references: 18927303
references: Nucleic Acids Res. 2010 Oct;38(18):e178
references: 20802226
references: Cancer Res. 2012 Oct 1;72(19):4890-5
references: 23002203
references: Genome Biol. 2013 Feb 14;14(2):R12
references: 23409703
references: Clin Cancer Res. 2012 Aug 15;18(16):4449-57
references: 22661537
references: Curr Med Chem. 2011;18(14):2146-57
references: 21517764
references: PLoS Genet. 2013 Apr;9(4):e1003464
references: 23637631
references: N Engl J Med. 2014 Nov 20;371(21):1963-71
references: 25264305
references: Bioinformatics. 2012 Aug 15;28(16):2114-21
references: 22711792
references: J Natl Cancer Inst. 1960 Jul;25:85-109
references: 14427847
references: Int J Cancer. 2006 Mar 1;118(5):1181-6
references: 16161041
references: Mod Pathol. 2011 Mar;24(3):430-42
references: 21076462
references: PLoS Comput Biol. 2012;8(4):e1002464
references: 22496636
references: Blood. 2006 Oct 1;108(7):2332-8
references: 16772610
references: Oncologist. 2013;18(7):865-75
references: 23814043
references: Proteomics. 2008 Nov;8(21):4433-43
references: 18846511
references: Bioinformatics. 2011 Apr 15;27(8):1068-75
references: 21330288
references: Cancer. 2013 May 1;119(9):1627-35
references: 23400546
references: Nat Rev Cancer. 2013 Nov;13(11):772-87
references: 24132104
references: Blood. 1988 Aug;72(2):567-72
references: 3165295
references: Bioinformatics. 2012 Dec 15;28(24):3232-9
references: 23093608
references: Cancer Biol Ther. 2007 Jan;6(1):40-5
references: 17172822
references: Genes Chromosomes Cancer. 2002 Aug;34(4):354-62
references: 12112524
references: Lab Invest. 2001 Mar;81(3):419-26
references: 11310834
references: PLoS One. 2012;7(6):e39987
references: 22761941
references: Genes Chromosomes Cancer. 2012 Jun;51(6):590-7
references: 22334442
references: Chin J Cancer. 2013 Nov;32(11):594-603
references: 24206917
references: Nat Genet. 2013 Jun;45(6):602-12
references: 23583981
references: Nat Biotechnol. 2013 Nov;31(11):1023-31
references: 24142049
references: Nat Genet. 2014 May;46(5):444-450
references: 24705251
references: Blood. 2001 Aug 15;98(4):1209-16
references: 11493472
references: Nat Commun. 2014;5:3116
references: 24445538
references: N Engl J Med. 2013 Jun 20;368(25):2385-94
references: 23724913
references: Biomed Res Int. 2013;2013:340620
references: 23555082
references: Cancer. 2014 Mar 15;120(6):799-807
references: 24327398
references: Bioinformatics. 2013 Apr 15;29(8):1004-10
references: 23457040
references: Histopathology. 2013 Dec;63(6):881-3
references: 23957430
references: Clin Lung Cancer. 2014 Nov;15(6):470-4
references: 25087901
references: Nat Commun. 2014 Sep 10;5:4846
references: 25204415
references: Clin Cancer Res. 2009 May 1;15(9):3143-9
references: 19383809
references: Expert Rev Hematol. 2014 Jun;7(3):347-57
references: 24720386
references: Oncogene. 2015 Jul;34(29):3815-25
references: 25263440
references: N Engl J Med. 2010 Oct 28;363(18):1693-703
references: 20979469
references: Clin Cancer Res. 2011 Dec 1;17(23):7394-401
references: 21948233
references: PLoS One. 2011 Jan 06;6(1):e15640
references: 21253578
references: Mod Pathol. 2007 May;20(5):538-44
references: 17334343
references: BMC Cancer. 2012 Sep 17;12:411
references: 22985168
references: Oncogene. 1994 Jun;9(6):1567-74
references: 8183550
references: Nat Biotechnol. 2013 Jul;31(7):630-7
references: 23811600
references: Genet Med. 2011 Jul;13(7):607-16
references: 21546842
references: Genome Biol. 2010;11(10):R104
references: 20964841
references: Cancer Sci. 2013 Nov;104(11):1396-400
references: 23991695
references: N Engl J Med. 2014 Sep 11;371(11):1005-15
references: 25207766
references: Dev Cell. 2012 Mar 13;22(3):489-500
references: 22421041
references: Bioinformatics. 2011 Jul 15;27(14):1922-8
references: 21593131
references: Oncogene. 2005 May 26;24(23 ):3847-52
references: 15750627
references: Cancer Cell. 2009 Nov 6;16(5):401-12
references: 19878872
references: Cancer Res. 2011 Feb 1;71(3):1060-70
references: 21148487
references: PLoS One. 2013 Dec 13;8(12):e82236
references: 24349229
references: Oncogene. 2012 Mar 8;31(10):1334-40
references: 21804605
references: Blood. 2003 Oct 1;102(7):2638-41
references: 12750159
references: Nat Med. 2012 Feb 12;18(3):382-4
references: 22327622
references: Blood. 1997 Feb 15;89(4):1394-404
references: 9028963
references: Oncogene Res. 1989;5(2):91-100
references: 2691958
references: Genes Chromosomes Cancer. 2003 Aug;37(4):427-32
references: 12800156
references: Blood. 2011 Jun 30;117(26):6999-7006
references: 21467543
references: Genome Biol. 2009;10(7):311
references: 19664186
references: Science. 2005 Oct 28;310(5748):644-8
references: 16254181
references: N Engl J Med. 2006 Dec 7;355(23):2408-17
references: 17151364
references: Haematologica. 2011 Mar;96(3):464-7
references: 21134980
references: Clin Cancer Res. 2007 Sep 1;13(17):5103-8
references: 17785564
references: Genes Chromosomes Cancer. 2003 May;37(1):98-105
references: 12661011
references: Nat Rev Genet. 2011 Jun 17;12(7):487-98
references: 21681210
references: Br J Cancer. 2007 Dec 17;97(12):1690-5
references: 17971772
references: Genome Biol. 2011;12(1):R6
references: 21247443
references: Clin Adv Hematol Oncol. 2014 Jul;12(7):429-39
references: 25322323
references: Oncol Rep. 2007 May;17(5):1033-6
references: 17390040
references: Nature. 2007 Aug 2;448(7153):561-6
references: 17625570
references: Am J Surg Pathol. 2010 May;34(5):599-608
references: 20410810
references: Prostate. 2014 Nov;74(15):1481-7
references: 25175352