Detecting and targetting oncogenic fusion proteins in the genomic era

Biology of the Cell

Volumn 107, Issue 5, 2015, Pages 111-129

  Davare, Monika A ^a,b   Tognon, Cristina E ^a,c  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

Cancer; Oncology cancer; Other receptors; Protein kinases phosphatases; Targeted therapy

Indexed keywords

ALECTINIB; BORTEZOMIB; CERITINIB; CRIZOTINIB; FORETINIB; HYBRID PROTEIN; IMATINIB; ONCOPROTEIN; PHOSPHOTRANSFERASE;

ARTICLE; CYTOGENETICS; GENOMICS; HUMAN; NEOPLASM; NEXT GENERATION SEQUENCING; ONCOGENE; PATHOGENESIS; PHOSPHOPROTEOMICS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEOMICS; ANIMAL; BIOLOGY; CHROMOSOME MAP; GENE EXPRESSION PROFILING; GENETICS; NEOPLASMS;

ANIMALS; CHROMOSOME MAPPING; COMPUTATIONAL BIOLOGY; GENE EXPRESSION PROFILING; GENOMICS; HUMANS; NEOPLASMS; ONCOGENE PROTEINS, FUSION;

EID: 84928762191     PISSN: 02484900     EISSN: 1768322X     Source Type: Journal    
DOI: 10.1111/boc.201400096     Document Type: Article

References (152)

1. Abate, F., Acquaviva, A., Paciello, G., Foti, C., Ficarra, E., Ferrarini, A., Delledonne, M., Iacobucci, I., Soverini, S., Martinelli, G. and Macii, E. (2012) Bellerophontes: An RNA-Seq data analysis framework for chimeric transcripts discovery based on accurate fusion model. Bioinformatics 28, 2114-2121
2. Abate, F., Zairis, S., Ficarra, E., Acquaviva, A., Wiggins, C.H., Frattini, V., Lasorella, A., Iavarone, A., Inghirami, G. and Rabadan, R. (2014) Pegasus: A comprehensive annotation and prediction tool for detection of driver gene fusions in cancer. BMC Syst. Biol. 8, 97
3. Ardini, E., Bosotti, R., Borgia, A.L., DePonti, C., Somaschini, A., Cammarota, R., Amboldi, N., Raddrizzani, L., Milani, A., Magnaghi, P., Ballinari, D., Casero, D., Gasparri, F., Banfi, P., Avanzi, N., Saccardo, M.B., Alzani, R., Bandiera, T., Felder, E., Donati, D., Pesenti, E., Sartore-Bianchi, A., Gambacorta, M., Pierotti, M.A., Siena, S., Veronese, S., Galvani, A. and Isacchi, A. (2014) The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Mol. Oncol 8(8), 1495-1507.
4. Asmann, Y.W., Hossain, A., Necela, B.M., Middha, S., Kalari, K.R., Sun, Z., Chai, H.S., Williamson, D.W., Radisky, D., Schroth, G.P., Kocher, J.P., Perez, E.A. and Thompson, E.A. (2011) A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines. Nucleic Acids Res. 39, e100
5. Awad, M.M., Katayama, R., McTigue, M., Liu, W., Deng, Y.L., Brooun, A., Friboulet, L., Huang, D., Falk, M.D., Timofeevski, S., Wilner, K.D., Lockerman, E.L., Khan, T.M., Mahmood, S., Gainor, J.F., Digumarthy, S.R., Stone, J.R., Mino-Kenudson, M., Christensen, J.G., Iafrate, A.J., Engelman, J.A. and Shaw, A.T. (2013) Acquired resistance to crizotinib from a mutation in CD74-ROS1. New Engl. J. Med. 368, 2395-2401
6. Awad, M.M. and Shaw, A.T. (2014) ALK inhibitors in non-small cell lung cancer: Crizotinib and beyond. Clin. Adv. Hematol. Oncol. 12, 429-439
7. Beccuti, M., Carrara, M., Cordero, F., Donatelli, S. and Calogero, R.A. (2013) The structure of state-of-art gene fusion-finder algorithms. Genome Bioinformatics 01;1(1), 2
8. Benelli, M., Pescucci, C., Marseglia, G., Severgnini, M., Torricelli, F. and Magi, A. (2012) Discovering chimeric transcripts in paired-end RNA-seq data by using EricScript. Bioinformatics 28, 3232-3239
9. Birch, A.H., Arcand, S.L., Oros, K.K., Rahimi, K., Watters, A.K., Provencher, D., Greenwood, C.M., Mes-Masson, A.M. and Tonin, P.N. (2011) Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours. PloS One 6, e28250
10. Birchmeier, C., Sharma, S. and Wigler, M. (1987) Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proc. Natl. Acad. Sci. U.S.A. 84, 9270-9274
11. Boehm, J.S. and Hahn, W.C. (2011) Towards systematic functional characterization of cancer genomes. Nat. Rev. Genet. 12, 487-498
12. Bradeen, H.A., Eide, C.A., O'Hare, T., Johnson, K.J., Willis, S.G., Lee, F.Y., Druker, B.J. and Deininger, M.W. (2006) Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: High efficacy of drug combinations. Blood 108, 2332-2338
13. Bridge, J.A., Kanamori, M., Ma, Z., Pickering, D., Hill, D.A., Lydiatt, W., Lui, M.Y., Colleoni, G.W., Antonescu, C.R., Ladanyi, M. and Morris, S.W. (2001) Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. Am. J. Pathol. 159, 411-415
14. Camidge, D.R., Pao, W. and Sequist, L.V. (2014) Acquired resistance to TKIs in solid tumours: Learning from lung cancer. Nat. Rev. Clin. Oncol. 11, 473-481
15. Carrara, M., Beccuti, M., Lazzarato, F., Cavallo, F., Cordero, F., Donatelli, S. and Calogero, R.A. (2013) State-of-the-art fusion-finder algorithms sensitivity and specificity. BioMed Res. Int. 2013, 340620
16. Casaluce, F., Sgambato, A., Maione, P., Rossi, A., Ferrara, C., Napolitano, A., Palazzolo, G., Ciardiello, F. and Gridelli, C. (2013) ALK inhibitors: A new targeted therapy in the treatment of advanced NSCLC. Targeted Oncol. 8, 55-67
17. Charest, A., Kheifets, V., Park, J., Lane, K., McMahon, K., Nutt, C.L. and Housman, D. (2003a) Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma. Proc. Natl. Acad. Sci. U.S.A. 100, 916-921
18. Charest, A., Lane, K., McMahon, K., Park, J., Preisinger, E., Conroy, H. and Housman, D. (2003b) Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). Genes Chromosomes Cancer 37, 58-71
19. Chi, H.T., Ly, B.T., Kano, Y., Tojo, A., Watanabe, T. and Sato, Y. (2012) ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412. Biochem. Biophys. Res. Commun. 429, 87-92
20. Chiari, R., Buttitta, F., Iacono, D., Bennati, C., Metro, G., Di Lorito, A., Iezzi, M., Tiseo, M., Mazzoni, F., Cappuzzo, F., Marchetti, A. and Crino, L. (2014) Dramatic response to crizotinib in ROS1 fluorescent in situ hybridization- and immunohistochemistry-positive lung adenocarcinoma: A case series. Clin. Lung Cancer 15, 470-474
21. Chu, H.T., Hsiao, W.W., Chen, J.C., Yeh, T.J., Tsai, M.H., Lin, H., Liu, Y.W., Lee, S.A., Chen, C.C., Tsao, T.T. and Kao, C.Y. (2013) EBARDenovo: Highly accurate de novo assembly of RNA-Seq with efficient chimera-detection. Bioinformatics 29, 1004-1010
22. Colleoni, G.W., Bridge, J.A., Garicochea, B., Liu, J., Filippa, D.A. and Ladanyi, M. (2000) ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35). Am. J. Pathol. 156, 781-789
23. Cools, J., Wlodarska, I., Somers, R., Mentens, N., Pedeutour, F., Maes, B., DeWolf-Peeters, C., Pauwels, P., Hagemeijer, A. and Marynen, P. (2002) Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 34, 354-362
24. Cunha, S.I. and Pietras, K. (2011) ALK1 as an emerging target for antiangiogenic therapy of cancer. Blood 117, 6999-7006
25. Davare, M.A., Saborowski, A., Eide, C.A., Tognon, C., Smith, R.L., Elferich, J., Agarwal, A., Tyner, J.W., Shinde, U.P., Lowe, S.W. and Druker, B.J. (2013) Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins. Proc. Natl. Acad. Sci. U.S.A. 110, 19519-19524
26. Davies, K.D. and Doebele, R.C. (2013) Molecular pathways: ROS1 fusion proteins in cancer. Clin. Cancer Res. 19, 4040-4045
27. Davies, K.D., Mahale, S., Astling, D.P., Aisner, D.L., Le, A.T., Hinz, T.K., Vaishnavi, A., Bunn, P.A., Jr., Heasley, L.E., Tan, A.C., Camidge, D.R., Varella-Garcia, M. and Doebele, R.C. (2013) Resistance to ROS1 inhibition mediated by EGFR pathway activation in non-small cell lung cancer. PloS One 8, e82236
28. DeBraekeleer, E., Douet-Guilbert, N. and DeBraekeleer, M. (2014) RARA fusion genes in acute promyelocytic leukemia: A review. Expert Rev. Hematol. 7, 347-357
29. DePaepe, P., Baens, M., vanKrieken, H., Verhasselt, B., Stul, M., Simons, A., Poppe, B., Laureys, G., Brons, P., Vandenberghe, P., Speleman, F., Praet, M., DeWolf-Peeters, C., Marynen, P. and Wlodarska, I. (2003) ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma. Blood 102, 2638-2641
30. Debelenko, L.V., Arthur, D.C., Pack, S.D., Helman, L.J., Schrump, D.S. and Tsokos, M. (2003) Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor. Lab. Invest. 83, 1255-1265
31. Debelenko, L.V., Raimondi, S.C., Daw, N., Shivakumar, B.R., Huang, D., Nelson, M. and Bridge, J.A. (2011) Renal cell carcinoma with novel VCL-ALK fusion: New representative of ALK-associated tumor spectrum. Modern Pathol. 24, 430-442
32. Doebele, R.C., Pilling, A.B., Aisner, D.L., Kutateladze, T.G., Le, A.T., Weickhardt, A.J., Kondo, K.L., Linderman, D.J., Heasley, L.E., Franklin, W.A., Varella-Garcia, M. and Camidge, D.R. (2012) Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin. Cancer Res. 18, 1472-1482
33. Drexler, H.G., Gignac, S.M., vonWasielewski, R., Werner, M. and Dirks, W.G. (2000) Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. Leukemia 14, 1533-1559
34. Drilon, A., Wang, L., Hasanovic, A., Suehara, Y., Lipson, D., Stephens, P., Ross, J., Miller, V., Ginsberg, M., Zakowski, M.F., Kris, M.G., Ladanyi, M. and Rizvi, N. (2013) Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov. 3, 630-635
35. Druker, B.J. (2009) Perspectives on the development of imatinib and the future of cancer research. Nat. Med. 15, 1149-1152
36. Druker, B.J., Guilhot, F., O'Brien, S.G., Gathmann, I., Kantarjian, H., Gattermann, N., Deininger, M.W., Silver, R.T., Goldman, J.M., Stone, R.M., Cervantes, F., Hochhaus, A., Powell, B.L., Gabrilove, J.L., Rousselot, P., Reiffers, J., Cornelissen, J.J., Hughes, T., Agis, H., Fischer, T., Verhoef, G., Shepherd, J., Saglio, G., Gratwohl, A., Nielsen, J.L., Radich, J.P., Simonsson, B., Taylor, K., Baccarani, M., So, C., Letvak, L., Larson, R.A. and Investigators, I. (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. New Engl. J. Med. 355, 2408-2417
37. Edgren, H., Murumagi, A., Kangaspeska, S., Nicorici, D., Hongisto, V., Kleivi, K., Rye, I.H., Nyberg, S., Wolf, M., Borresen-Dale, A.L. and Kallioniemi, O. (2011) Identification of fusion genes in breast cancer by paired-end RNA-sequencing. Genome Biol. 12, R6
38. Fehr, A., Loning, T. and Stenman, G. (2011) Mammary analogue secretory carcinoma of the salivary glands with ETV6-NTRK3 gene fusion. Am. J. Surg. Pathol. 35, 1600-1602
39. Frampton, G.M., Fichtenholtz, A., Otto, G.A., Wang, K., Downing, S.R., He, J., Schnall-Levin, M., White, J., Sanford, E.M., An, P., Sun, J., Juhn, F., Brennan, K., Iwanik, K., Maillet, A., Buell, J., White, E., Zhao, M., Balasubramanian, S., Terzic, S., Richards, T., Banning, V., Garcia, L., Mahoney, K., Zwirko, Z., Donahue, A., Beltran, H., Mosquera, J.M., Rubin, M.A., Dogan, S., Hedvat, C.V., Berger, M.F., Pusztai, L., Lechner, M., Boshoff, C., Jarosz, M., Vietz, C., Parker, A., Miller, V.A., Ross, J.S., Curran, J., Cronin, M.T., Stephens, P.J., Lipson, D. and Yelensky, R. (2013) Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat. Biotechnol. 31, 1023-1031
40. Francis, R.W., Thompson-Wicking, K., Carter, K.W., Anderson, D., Kees, U.R. and Beesley, A.H. (2012) FusionFinder: A software tool to identify expressed gene fusion candidates from RNA-Seq data. PloS One 7, e39987
41. Gainor, J.F. and Shaw, A.T. (2013) Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 18, 865-875
42. Ge, H., Liu, K., Juan, T., Fang, F., Newman, M. and Hoeck, W. (2011) FusionMap: Detecting fusion genes from next-generation sequencing data at base-pair resolution. Bioinformatics 27, 1922-1928
43. Giacomini, C.P., Sun, S., Varma, S., Shain, A.H., Giacomini, M.M., Balagtas, J., Sweeney, R.T., Lai, E., Del Vecchio, C.A., Forster, A.D., Clarke, N., Montgomery, K.D., Zhu, S., Wong, A.J., vande Rijn, M., West, R.B. and Pollack, J.R. (2013) Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types. PLoS Genet. 9, e1003464
44. Gibbons, D.L., Pricl, S., Kantarjian, H., Cortes, J. and Quintas-Cardama, A. (2012) The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm. Cancer 118, 293-299
45. Grande, E., Bolos, M.V. and Arriola, E. (2011) Targeting oncogenic ALK: A promising strategy for cancer treatment. Mol. Cancer Ther. 10, 569-579
46. Greco, A., Mariani, C., Miranda, C., Pagliardini, S. and Pierotti, M.A. (1993) Characterization of the NTRK1 genomic region involved in chromosomal rearrangements generating TRK oncogenes. Genomics 18, 397-400
47. Gu, T.L., Deng, X., Huang, F., Tucker, M., Crosby, K., Rimkunas, V., Wang, Y., Deng, G., Zhu, L., Tan, Z., Hu, Y., Wu, C., Nardone, J., MacNeill, J., Ren, J., Reeves, C., Innocenti, G., Norris, B., Yuan, J., Yu, J., Haack, H., Shen, B., Peng, C., Li, H., Zhou, X., Liu, X., Rush, J. and Comb, M.J. (2011) Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PloS One 6, e15640
48. Hanahan, D. and Weinberg, R.A. (2000) The hallmarks of cancer. Cell 100, 57-70
49. Hantschel, O., Grebien, F. and Superti-Furga, G. (2012) The growing arsenal of ATP-competitive and allosteric inhibitors of BCR-ABL. Cancer Res. 72, 4890-4895
50. Hernandez, L., Pinyol, M., Hernandez, S., Bea, S., Pulford, K., Rosenwald, A., Lamant, L., Falini, B., Ott, G., Mason, D.Y., Delsol, G. and Campo, E. (1999) TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. Blood 94, 3265-3268
51. Hessels, D., Smit, F.P., Verhaegh, G.W., Witjes, J.A., Cornel, E.B. and Schalken, J.A. (2007) Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin. Cancer Res. 13, 5103-5108
52. Heuckmann, J.M., Holzel, M., Sos, M.L., Heynck, S., Balke-Want, H., Koker, M., Peifer, M., Weiss, J., Lovly, C.M., Grutter, C., Rauh, D., Pao, W. and Thomas, R.K. (2011) ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin. Cancer Res. 17, 7394-7401
53. Huang, E.J. and Reichardt, L.F. (2001) Neurotrophins: Roles in neuronal development and function. Ann. Rev. Neurosci. 24, 677-736
54. Huang, M.E., Ye, Y.C., Chen, S.R., Chai, J.R., Lu, J.X., Zhoa, L., Gu, L.J. and Wang, Z.Y. (1988) Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72, 567-572
55. Iyer, M.K., Chinnaiyan, A.M. and Maher, C.A. (2011) ChimeraScan: A tool for identifying chimeric transcription in sequencing data. Bioinformatics 27, 2903-2904
56. Jia, W., Qiu, K., He, M., Song, P., Zhou, Q., Zhou, F., Yu, Y., Zhu, D., Nickerson, M.L., Wan, S., Liao, X., Zhu, X., Peng, S., Li, Y., Wang, J. and Guo, G. (2013) SOAPfuse: An algorithm for identifying fusion transcripts from paired-end RNA-Seq data. Genome Biol. 14, R12
57. Jones, D.T., Hutter, B., Jager, N., Korshunov, A., Kool, M., Warnatz, H.J., Zichner, T., Lambert, S.R., Ryzhova, M., Quang, D.A., Fontebasso, A.M., Stutz, A.M., Hutter, S., Zuckermann, M., Sturm, D., Gronych, J., Lasitschka, B., Schmidt, S., Seker-Cin, H., Witt, H., Sultan, M., Ralser, M., Northcott, P.A., Hovestadt, V., Bender, S., Pfaff, E., Stark, S., Faury, D., Schwartzentruber, J., Majewski, J., Weber, U.D., Zapatka, M., Raeder, B., Schlesner, M., Worth, C.L., Bartholomae, C.C., vonKalle, C., Imbusch, C.D., Radomski, S., Lawerenz, C., vanSluis, P., Koster, J., Volckmann, R., Versteeg, R., Lehrach, H., Monoranu, C., Winkler, B., Unterberg, A., Herold-Mende, C., Milde, T., Kulozik, A.E., Ebinger, M., Schuhmann, M.U., Cho, Y.J., Pomeroy, S.L., vonDeimling, A., Witt, O., Taylor, M.D., Wolf, S., Karajannis, M.A., Eberhart, C.G., Scheurlen, W., Hasselblatt, M., Ligon, K.L., Kieran, M.W., Korbel, J.O., Yaspo, M.L., Brors, B., Felsberg, J., Reifenberger, G., Collins, V.P., Jabado, N., Eils, R., Lichter, P., Pfister, S.M. and International Cancer Genome Consortium PedBrain Tumor, P. (2013) Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat. Genet. 45, 927-932
58. Jung, Y., Kim, P., Jung, Y., Keum, J., Kim, S.N., Choi, Y.S., Do, I.G., Lee, J., Choi, S.J., Kim, S., Lee, J.E., Kim, J., Lee, S. and Kim, J. (2012) Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing. Genes Chromosomes Cancer 51, 590-597
59. Katayama, R., Friboulet, L., Koike, S., Lockerman, E.L., Khan, T.M., Gainor, J.F., Iafrate, A.J., Takeuchi, K., Taiji, M., Okuno, Y., Fujita, N., Engelman, J.A. and Shaw, A.T. (2014) Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin. Cancer Res. 20, 5686-5696
60. Kim, D. and Salzberg, S.L. (2011) TopHat-Fusion: An algorithm for discovery of novel fusion transcripts. Genome Biol. 12, R72
61. Kim, J., Wu, L., Zhao, J.C., Jin, H.J. and Yu, J. (2014) TMPRSS2-ERG gene fusions induce prostate tumorigenesis by modulating microRNA miR-200c. Oncogene 33, 5183-5192
62. Kinsella, M., Harismendy, O., Nakano, M., Frazer, K.A. and Bafna, V. (2011) Sensitive gene fusion detection using ambiguously mapping RNA-Seq read pairs. Bioinformatics 27, 1068-1075
63. Knezevich, S.R., Garnett, M.J., Pysher, T.J., Beckwith, J.B., Grundy, P.E. and Sorensen, P.H. (1998a) ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 58, 5046-5048
64. Knezevich, S.R., McFadden, D.E., Tao, W., Lim, J.F. and Sorensen, P.H. (1998b) A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat. Genet. 18, 184-187
65. Kohno, T., Tsuta, K., Tsuchihara, K., Nakaoku, T., Yoh, K. and Goto, K. (2013) RET fusion gene: Translation to personalized lung cancer therapy. Cancer Sci. 104, 1396-1400
66. Kralik, J.M., Kranewitter, W., Boesmueller, H., Marschon, R., Tschurtschenthaler, G., Rumpold, H., Wiesinger, K., Erdel, M., Petzer, A.L. and Webersinke, G. (2011) Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia. Diagnostic Pathol. 6, 19
67. Kwak, E.L., Bang, Y.J., Camidge, D.R., Shaw, A.T., Solomon, B., Maki, R.G., Ou, S.H., Dezube, B.J., Janne, P.A., Costa, D.B., Varella-Garcia, M., Kim, W.H., Lynch, T.J., Fidias, P., Stubbs, H., Engelman, J.A., Sequist, L.V., Tan, W., Gandhi, L., Mino-Kenudson, M., Wei, G.C., Shreeve, S.M., Ratain, M.J., Settleman, J., Christensen, J.G., Haber, D.A., Wilner, K., Salgia, R., Shapiro, G.I., Clark, J.W. and Iafrate, A.J. (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New Engl. J. Med. 363, 1693-1703
68. Lamant, L., Gascoyne, R.D., Duplantier, M.M., Armstrong, F., Raghab, A., Chhanabhai, M., Rajcan-Separovic, E., Raghab, J., Delsol, G. and Espinos, E. (2003) Non-muscle myosin heavy chain (MYH9): A new partner fused to ALK in anaplastic large cell lymphoma. Genes Chromosomes Cancer 37, 427-432
69. Larrivee, B., Prahst, C., Gordon, E., del Toro, R., Mathivet, T., Duarte, A., Simons, M. and Eichmann, A. (2012) ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway. Dev. Cell 22, 489-500
70. Lawrence, B., Perez-Atayde, A., Hibbard, M.K., Rubin, B.P., Dal Cin, P., Pinkus, J.L., Pinkus, G.S., Xiao, S., Yi, E.S., Fletcher, C.D. and Fletcher, J.A. (2000) TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am. J. Pathol. 157, 377-384
71. Lee, J., Lee, S.E., Kang, S.Y., Do, I.G., Lee, S., Ha, S.Y., Cho, J., Kang, W.K., Jang, J., Ou, S.H. and Kim, K.M. (2013) Identification of ROS1 rearrangement in gastric adenocarcinoma. Cancer 119, 1627-1635
72. Leeman-Neill, R.J., Kelly, L.M., Liu, P., Brenner, A.V., Little, M.P., Bogdanova, T.I., Evdokimova, V.N., Hatch, M., Zurnadzy, L.Y., Nikiforova, M.N., Yue, N.J., Zhang, M., Mabuchi, K., Tronko, M.D. and Nikiforov, Y.E. (2014) ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer 120, 799-807
73. Li, Y., Chien, J., Smith, D.I. and Ma, J. (2011) FusionHunter: Identifying fusion transcripts in cancer using paired-end RNA-seq. Bioinformatics 27, 1708-1710
74. Li, Z., Tognon, C.E., Godinho, F.J., Yasaitis, L., Hock, H., Herschkowitz, J.I., Lannon, C.L., Cho, E., Kim, S.J., Bronson, R.T., Perou, C.M., Sorensen, P.H. and Orkin, S.H. (2007) ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Cancer Cell 12, 542-558
75. Lin, E., Li, L., Guan, Y., Soriano, R., Rivers, C.S., Mohan, S., Pandita, A., Tang, J. and Modrusan, Z. (2009) Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol. Cancer Res. 7, 1466-1476
76. Lipson, D., Capelletti, M., Yelensky, R., Otto, G., Parker, A., Jarosz, M., Curran, J.A., Balasubramanian, S., Bloom, T., Brennan, K.W., Donahue, A., Downing, S.R., Frampton, G.M., Garcia, L., Juhn, F., Mitchell, K.C., White, E., White, J., Zwirko, Z., Peretz, T., Nechushtan, H., Soussan-Gutman, L., Kim, J., Sasaki, H., Kim, H.R., Park, S.I., Ercan, D., Sheehan, C.E., Ross, J.S., Cronin, M.T., Janne, P.A. and Stephens, P.J. (2012) Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat. Med. 18, 382-384
77. Liu, H., Westergard, T.D., Cashen, A., Piwnica-Worms, D.R., Kunkle, L., Vij, R., Pham, C.G., DiPersio, J., Cheng, E.H. and Hsieh, J.J. (2014) Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL leukemias through MLL-AF4. Cancer Cell 25, 530-542
78. Lovly, C.M. and Pao, W. (2012) Escaping ALK inhibition: Mechanisms of and strategies to overcome resistance. Sci. Transl. Med. 4, 120ps122
79. Lu, X.Y., Cai, Q. and Ding, K. (2011) Recent developments in the third generation inhibitors of Bcr-Abl for overriding T315I mutation. Curr. Med. Chem. 18, 2146-2157
80. Ma, Z., Hill, D.A., Collins, M.H., Morris, S.W., Sumegi, J., Zhou, M., Zuppan, C. and Bridge, J.A. (2003) Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 37, 98-105
81. Martin, M.J., Melnyk, N., Pollard, M., Bowden, M., Leong, H., Podor, T.J., Gleave, M. and Sorensen, P.H. (2006) The insulin-like growth factor I receptor is required for Akt activation and suppression of anoikis in cells transformed by the ETV6-NTRK3 chimeric tyrosine kinase. Mol. Cell. Biol. 26, 1754-1769
82. McDonald, J., Bayrak-Toydemir, P. and Pyeritz, R.E. (2011) Hereditary hemorrhagic telangiectasia: An overview of diagnosis, management, and pathogenesis. Genet. Med. 13, 607-616
83. McPherson, A., Hormozdiari, F., Zayed, A., Giuliany, R., Ha, G., Sun, M.G., Griffith, M., Heravi Moussavi, A., Senz, J., Melnyk, N., Pacheco, M., Marra, M.A., Hirst, M., Nielsen, T.O., Sahinalp, S.C., Huntsman, D. and Shah, S.P. (2011a) deFuse: An algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput. Biol. 7, e1001138
84. McPherson, A., Wu, C., Hajirasouliha, I., Hormozdiari, F., Hach, F., Lapuk, A., Volik, S., Shah, S., Collins, C. and Sahinalp, S.C. (2011b) Comrad: Detection of expressed rearrangements by integrated analysis of RNA-Seq and low coverage genome sequence data. Bioinformatics 27, 1481-1488
85. McPherson, A., Wu, C., Wyatt, A.W., Shah, S., Collins, C. and Sahinalp, S.C. (2012) nFuse: Discovery of complex genomic rearrangements in cancer using high-throughput sequencing. Genome Res. 22, 2250-2261
86. Meech, S.J., McGavran, L., Odom, L.F., Liang, X., Meltesen, L., Gump, J., Wei, Q., Carlsen, S. and Hunger, S.P. (2001) Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4-anaplastic lymphoma kinase gene fusion. Blood 98, 1209-1216
87. Mehra, R., Tomlins, S.A., Shen, R., Nadeem, O., Wang, L., Wei, J.T., Pienta, K.J., Ghosh, D., Rubin, M.A., Chinnaiyan, A.M. and Shah, R.B. (2007) Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod. Pathol. 20, 538-544
88. Mian, A.A., Metodieva, A., Badura, S., Khateb, M., Ruimi, N., Najajreh, Y., Ottmann, O.G., Mahajna, J. and Ruthardt, M. (2012) Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I. BMC Cancer 12, 411
89. Morris, S.W., Kirstein, M.N., Valentine, M.B., Dittmer, K.G., Shapiro, D.N., Saltman, D.L. and Look, A.T. (1994) Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 263, 1281-1284
90. Mounir, Z., Lin, F., Lin, V.G., Korn, J.M., Yu, Y., Valdez, R., Aina, O.H., Buchwalter, G., Jaffe, A.B., Korpal, M., Zhu, P., Brown, M., Cardiff, R.D., Rocnik, J.L., Yang, Y. and Pagliarini, R. (2014) TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation. Oncogene, doi: 10.1038/onc.2014.308
91. Nakagawara, A. (2001) Trk receptor tyrosine kinases: A bridge between cancer and neural development. Cancer Lett. 169, 107-114
92. Nam, R.K., Sugar, L., Wang, Z., Yang, W., Kitching, R., Klotz, L.H., Venkateswaran, V., Narod, S.A. and Seth, A. (2007a) Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression. Cancer Biol. Therapy 6, 40-45
93. Nam, R.K., Sugar, L., Yang, W., Srivastava, S., Klotz, L.H., Yang, L.Y., Stanimirovic, A., Encioiu, E., Neill, M., Loblaw, D.A., Trachtenberg, J., Narod, S.A. and Seth, A. (2007b) Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br. J. Cancer 97, 1690-1695
94. Nita-Lazar, A., Saito-Benz, H. and White, F.M. (2008) Quantitative phosphoproteomics by mass spectrometry: Past, present, and future. Proteomics 8, 4433-4443
95. Nowell, P.C. and Hungerford, D.A. (1960) Chromosome studies on normal and leukemic human leukocytes. J. Natl. Cancer Institute 25, 85-109
96. O'Hare, T., Eide, C.A. and Deininger, M.W. (2007a) Bcr-Abl kinase domain mutations and the unsettled problem of Bcr-AblT315I: Looking into the future of controlling drug resistance in chronic myeloid leukemia. Clin. Lymphoma Myeloma 7(Suppl 3), S120-130
97. O'Hare, T., Eide, C.A. and Deininger, M.W. (2007b). Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 110, 2242-2249
98. O'Hare, T., Shakespeare, W.C., Zhu, X., Eide, C.A., Rivera, V.M., Wang, F., Adrian, L.T., Zhou, T., Huang, W.S., Xu, Q., Metcalf, C.A., 3rd, Tyner, J.W., Loriaux, M.M., Corbin, A.S., Wardwell, S., Ning, Y., Keats, J.A., Wang, Y., Sundaramoorthi, R., Thomas, M., Zhou, D., Snodgrass, J., Commodore, L., Sawyer, T.K., Dalgarno, D.C., Deininger, M.W., Druker, B.J. and Clackson, T. (2009) AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16, 401-412
99. Panagopoulos, I., Nilsson, T., Domanski, H.A., Isaksson, M., Lindblom, P., Mertens, F. and Mandahl, N. (2006) Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. Int. J. Cancer 118, 1181-1186
100. Parker, B.C. and Zhang, W. (2013) Fusion genes in solid tumors: An emerging target for cancer diagnosis and treatment. Chin. J. Cancer 32, 594-603
101. Perot, G., Soubeyran, I., Ribeiro, A., Bonhomme, B., Savagner, F., Boutet-Bouzamondo, N., Hostein, I., Bonichon, F., Godbert, Y. and Chibon, F. (2014) Identification of a recurrent STRN/ALK fusion in thyroid carcinomas. PloS One 9, e87170
102. Petrovics, G., Liu, A., Shaheduzzaman, S., Furusato, B., Sun, C., Chen, Y., Nau, M., Ravindranath, L., Chen, Y., Dobi, A., Srikantan, V., Sesterhenn, I.A., McLeod, D.G., Vahey, M., Moul, J.W. and Srivastava, S. (2005) Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome. Oncogene 24, 3847-3852
103. Piazza, R., Pirola, A., Spinelli, R., Valletta, S., Redaelli, S., Magistroni, V. and Gambacorti-Passerini, C. (2012) FusionAnalyser: A new graphical, event-driven tool for fusion rearrangements discovery. Nucleic Acids Res. 40, e123
104. Pulford, K., Lamant, L., Morris, S.W., Butler, L.H., Wood, K.M., Stroud, D., Delsol, G. and Mason, D.Y. (1997) Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood 89, 1394-1404
105. Qadir, M.A., Zhan, S.H., Kwok, B., Bruestle, J., Drees, B., Popescu, O.E. and Sorensen, P.H. (2014) ChildSeq-RNA: A next-generation sequencing-based diagnostic assay to identify known fusion transcripts in childhood sarcomas. J. Mol. Diagn. 16, 361-370
106. Redmond, A.M. and Carroll, J.S. (2009) Defining and targeting transcription factors in cancer. Genome Biol. 10, 311
107. Ren, H., Tan, Z.P., Zhu, X., Crosby, K., Haack, H., Ren, J.M., Beausoleil, S., Moritz, A., Innocenti, G., Rush, J., Zhang, Y., Zhou, X.M., Gu, T.L., Yang, Y.F. and Comb, M.J. (2012) Identification of anaplastic lymphoma kinase as a potential therapeutic target in ovarian cancer. Cancer Res. 72, 3312-3323
108. Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., Hu, Y., Tan, Z., Stokes, M., Sullivan, L., Mitchell, J., Wetzel, R., Macneill, J., Ren, J.M., Yuan, J., Bakalarski, C.E., Villen, J., Kornhauser, J.M., Smith, B., Li, D., Zhou, X., Gygi, S.P., Gu, T.L., Polakiewicz, R.D., Rush, J. and Comb, M.J. (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190-1203
109. Rimkunas, V.M., Crosby, K.E., Li, D., Hu, Y., Kelly, M.E., Gu, T.L., Mack, J.S., Silver, M.R., Zhou, X. and Haack, H. (2012) Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: Identification of a FIG-ROS1 fusion. Clin. Cancer Res. 18, 4449-4457
110. Roberts, K.G., Li, Y., Payne-Turner, D., Harvey, R.C., Yang, Y.L., Pei, D., McCastlain, K., Ding, L., Lu, C., Song, G., Ma, J., Becksfort, J., Rusch, M., Chen, S.C., Easton, J., Cheng, J., Boggs, K., Santiago-Morales, N., Iacobucci, I., Fulton, R.S., Wen, J., Valentine, M., Cheng, C., Paugh, S.W., Devidas, M., Chen, I.M., Reshmi, S., Smith, A., Hedlund, E., Gupta, P., Nagahawatte, P., Wu, G., Chen, X., Yergeau, D., Vadodaria, B., Mulder, H., Winick, N.J., Larsen, E.C., Carroll, W.L., Heerema, N.A., Carroll, A.J., Grayson, G., Tasian, S.K., Moore, A.S., Keller, F., Frei-Jones, M., Whitlock, J.A., Raetz, E.A., White, D.L., Hughes, T.P., Guidry Auvil, J.M., Smith, M.A., Marcucci, G., Bloomfield, C.D., Mrozek, K., Kohlschmidt, J., Stock, W., Kornblau, S.M., Konopleva, M., Paietta, E., Pui, C.H., Jeha, S., Relling, M.V., Evans, W.E., Gerhard, D.S., Gastier-Foster, J.M., Mardis, E., Wilson, R.K., Loh, M.L., Downing, J.R., Hunger, S.P., Willman, C.L., Zhang, J. and Mullighan, C.G. (2014) Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. New Engl. J. Med. 371, 1005-1015
111. Rodig, S.J. and Shapiro, G.I. (2010) Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases. Curr. Opin. Invest. Drugs 11, 1477-1490
112. Ross, J.S., Wang, K., Gay, L., Al-Rohil, R., Rand, J.V., Jones, D.M., Lee, H.J., Sheehan, C.E., Otto, G.A., Palmer, G., Yelensky, R., Lipson, D., Morosini, D., Hawryluk, M., Catenacci, D.V., Miller, V.A., Churi, C., Ali, S. and Stephens, P.J. (2014) New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist 19, 235-242
113. Rubin, B.P., Chen, C.J., Morgan, T.W., Xiao, S., Grier, H.E., Kozakewich, H.P., Perez-Atayde, A.R. and Fletcher, J.A. (1998) Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: Cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am. J. Pathol. 153, 1451-1458
114. Sakarya, O., Breu, H., Radovich, M., Chen, Y., Wang, Y.N., Barbacioru, C., Utiramerur, S., Whitley, P.P., Brockman, J.P., Vatta, P., Zhang, Z., Popescu, L., Muller, M.W., Kudlingar, V., Garg, N., Li, C.Y., Kong, B.S., Bodeau, J.P., Nutter, R.C., Gu, J., Bramlett, K.S., Ichikawa, J.K., Hyland, F.C. and Siddiqui, A.S. (2012) RNA-Seq mapping and detection of gene fusions with a suffix array algorithm. PLoS Comput. Biol. 8, e1002464
115. Saramaki, O.R., Harjula, A.E., Martikainen, P.M., Vessella, R.L., Tammela, T.L. and Visakorpi, T. (2008) TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin. Cancer Res. 14, 3395-3400
116. Sboner, A., Habegger, L., Pflueger, D., Terry, S., Chen, D.Z., Rozowsky, J.S., Tewari, A.K., Kitabayashi, N., Moss, B.J., Chee, M.S., Demichelis, F., Rubin, M.A. and Gerstein, M.B. (2010) FusionSeq: A modular framework for finding gene fusions by analyzing paired-end RNA-sequencing data. Genome Biol. 11, R104
117. Shah, N., Lankerovich, M., Lee, H., Yoon, J.G., Schroeder, B. and Foltz, G. (2013) Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data. BMC Genomics 14, 818
118. Sharma, S., Birchmeier, C., Nikawa, J., O'Neill, K., Rodgers, L. and Wigler, M. (1989) Characterization of the ros1-gene products expressed in human glioblastoma cell lines. Oncogene Res. 5, 91-100
119. Shaw, A.T., Hsu, P.P., Awad, M.M. and Engelman, J.A. (2013a) Tyrosine kinase gene rearrangements in epithelial malignancies. Nat. Rev. Cancer 13, 772-787
120. Shaw, A.T., Kim, D.W., Nakagawa, K., Seto, T., Crino, L., Ahn, M.J., DePas, T., Besse, B., Solomon, B.J., Blackhall, F., Wu, Y.L., Thomas, M., O'Byrne, K.J., Moro-Sibilot, D., Camidge, D.R., Mok, T., Hirsh, V., Riely, G.J., Iyer, S., Tassell, V., Polli, A., Wilner, K.D. and Janne, P.A. (2013b) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. New Engl. J. Med. 368, 2385-2394
121. Shaw, A.T., Ou, S.H., Bang, Y.J., Camidge, D.R., Solomon, B.J., Salgia, R., Riely, G.J., Varella-Garcia, M., Shapiro, G.I., Costa, D.B., Doebele, R.C., Le, L.P., Zheng, Z., Tan, W., Stephenson, P., Shreeve, S.M., Tye, L.M., Christensen, J.G., Wilner, K.D., Clark, J.W. and Iafrate, A.J. (2014) Crizotinib in ROS1-rearranged non-small-cell lung cancer. New Engl. J. Med. 371, 1963-1971
122. Shiota, M., Fujimoto, J., Semba, T., Satoh, H., Yamamoto, T. and Mori, S. (1994) Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene 9, 1567-1574
123. Skalova, A., Vanecek, T., Sima, R., Laco, J., Weinreb, I., Perez-Ordonez, B., Starek, I., Geierova, M., Simpson, R.H., Passador-Santos, F., Ryska, A., Leivo, I., Kinkor, Z. and Michal, M. (2010) Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: A hitherto undescribed salivary gland tumor entity. Am. J. Surg. Pathol. 34, 599-608
124. Soda, M., Choi, Y.L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S., Watanabe, H., Kurashina, K., Hatanaka, H., Bando, M., Ohno, S., Ishikawa, Y., Aburatani, H., Niki, T., Sohara, Y., Sugiyama, Y. and Mano, H. (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448, 561-566
125. Solomon, B.J., Mok, T., Kim, D.W., Wu, Y.L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., Iyer, S., Reisman, A., Wilner, K.D., Tursi, J., Blackhall, F. and Investigators, P. (2014) First-line crizotinib versus chemotherapy in ALK-positive lung cancer. New Engl. J. Med. 371, 2167-2177
126. Stransky, N., Cerami, E., Schalm, S., Kim, J.L. and Lengauer, C. (2014) The landscape of kinase fusions in cancer. Nat. Commun. 5, 4846
127. Suehara, Y., Arcila, M., Wang, L., Hasanovic, A., Ang, D., Ito, T., Kimura, Y., Drilon, A., Guha, U., Rusch, V., Kris, M.G., Zakowski, M.F., Rizvi, N., Khanin, R. and Ladanyi, M. (2012) Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions. Clin. Cancer Res. 18, 6599-6608
128. Sun, R., Love, M.I., Zemojtel, T., Emde, A.K., Chung, H.R., Vingron, M. and Haas, S.A. (2012) Breakpointer: Using local mapping artifacts to support sequence breakpoint discovery from single-end reads. Bioinformatics 28, 1024-1025
129. Taipale, M., Krykbaeva, I., Whitesell, L., Santagata, S., Zhang, J., Liu, Q., Gray, N.S. and Lindquist, S. (2013) Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells. Nat. Biotechnol. 31, 630-637
130. Takashima, T. and Misawa, S. (1992) [Retinoic acid receptor alpha gene in t (15; 17) APL]. Nihon rinsho. Jap. J. Clin. Med. 50, 1363-1368
131. Takeuchi, K., Choi, Y.L., Soda, M., Inamura, K., Togashi, Y., Hatano, S., Enomoto, M., Takada, S., Yamashita, Y., Satoh, Y., Okumura, S., Nakagawa, K., Ishikawa, Y. and Mano, H. (2008) Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin. Cancer Res. 14, 6618-6624
132. Takeuchi, K., Choi, Y.L., Togashi, Y., Soda, M., Hatano, S., Inamura, K., Takada, S., Ueno, T., Yamashita, Y., Satoh, Y., Okumura, S., Nakagawa, K., Ishikawa, Y. and Mano, H. (2009) KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin. Cancer Res. 15, 3143-3149
133. Takeuchi, K., Soda, M., Togashi, Y., Ota, Y., Sekiguchi, Y., Hatano, S., Asaka, R., Noguchi, M. and Mano, H. (2011) Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma. Haematologica 96, 464-467
134. Takeuchi, K., Soda, M., Togashi, Y., Suzuki, R., Sakata, S., Hatano, S., Asaka, R., Hamanaka, W., Ninomiya, H., Uehara, H., Lim Choi, Y., Satoh, Y., Okumura, S., Nakagawa, K., Mano, H. and Ishikawa, Y. (2012) RET, ROS1 and ALK fusions in lung cancer. Nat. Med. 18, 378-381
135. Taris, M., Irani, J., Blanchet, P., Multigner, L., Cathelineau, X. and Fromont, G. (2014) ERG expression in prostate cancer: The prognostic paradox. Prostate 74, 1481-1487
136. Thiele, C.J., Li, Z. and McKee, A.E. (2009) On Trk-the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin. Cancer Res. 15, 5962-5967
137. Togashi, Y., Soda, M., Sakata, S., Sugawara, E., Hatano, S., Asaka, R., Nakajima, T., Mano, H. and Takeuchi, K. (2012) KLC1-ALK: A novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PloS One 7, e31323
138. Tognon, C., Knezevich, S.R., Huntsman, D., Roskelley, C.D., Melnyk, N., Mathers, J.A., Becker, L., Carneiro, F., MacPherson, N., Horsman, D., Poremba, C. and Sorensen, P.H. (2002) Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2, 367-376
139. Tognon, C.E., Martin, M.J., Moradian, A., Trigo, G., Rotblat, B., Cheng, S.W., Pollard, M., Uy, E., Chow, C., Carboni, J.M., Gottardis, M.M., Pollak, M., Morin, G.B. and Sorensen, P.H. (2012) A tripartite complex composed of ETV6-NTRK3, IRS1 and IGF1R is required for ETV6-NTRK3-mediated membrane localization and transformation. Oncogene 31, 1334-1340
140. Tognon, C.E., Somasiri, A.M., Evdokimova, V.E., Trigo, G., Uy, E.E., Melnyk, N., Carboni, J.M., Gottardis, M.M., Roskelley, C.D., Pollak, M. and Sorensen, P.H. (2011) ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway. Cancer Res. 71, 1060-1070
141. Tomlins, S.A., Rhodes, D.R., Perner, S., Dhanasekaran, S.M., Mehra, R., Sun, X.W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., Lee, C., Montie, J.E., Shah, R.B., Pienta, K.J., Rubin, M.A. and Chinnaiyan, A.M. (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644-648
142. Tort, F., Pinyol, M., Pulford, K., Roncador, G., Hernandez, L., Nayach, I., Kluin-Nelemans, H.C., Kluin, P., Touriol, C., Delsol, G., Mason, D. and Campo, E. (2001) Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma. Lab. Invest. 81, 419-426
143. Vaishnavi, A., Capelletti, M., Le, A.T., Kako, S., Butaney, M., Ercan, D., Mahale, S., Davies, K.D., Aisner, D.L., Pilling, A.B., Berge, E.M., Kim, J., Sasaki, H., Park, S.I., Kryukov, G., Garraway, L.A., Hammerman, P.S., Haas, J., Andrews, S.W., Lipson, D., Stephens, P.J., Miller, V.A., Varella-Garcia, M., Janne, P.A. and Doebele, R.C. (2013) Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat. Med. 19, 1469-1472
144. Wang, K., Singh, D., Zeng, Z., Coleman, S.J., Huang, Y., Savich, G.L., He, X., Mieczkowski, P., Grimm, S.A., Perou, C.M., MacLeod, J.N., Chiang, D.Y., Prins, J.F. and Liu, J. (2010) MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Res. 38, e178
145. Wang, Q., Xia, J., Jia, P., Pao, W. and Zhao, Z. (2013) Application of next generation sequencing to human gene fusion detection: Computational tools, features and perspectives. Brief. Bioinformatics 14, 506-519
146. Wiesner, T., He, J., Yelensky, R., Esteve-Puig, R., Botton, T., Yeh, I., Lipson, D., Otto, G., Brennan, K., Murali, R., Garrido, M., Miller, V.A., Ross, J.S., Berger, M.F., Sparatta, A., Palmedo, G., Cerroni, L., Busam, K.J., Kutzner, H., Cronin, M.T., Stephens, P.J. and Bastian, B.C. (2014) Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat. Commun. 5, 3116
147. Winnes, M., Lissbrant, E., Damber, J.E. and Stenman, G. (2007) Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer. Oncol. Rep. 17, 1033-1036
148. Wu, G., Diaz, A.K., Paugh, B.S., Rankin, S.L., Ju, B., Li, Y., Zhu, X., Qu, C., Chen, X., Zhang, J., Easton, J., Edmonson, M., Ma, X., Lu, C., Nagahawatte, P., Hedlund, E., Rusch, M., Pounds, S., Lin, T., Onar-Thomas, A., Huether, R., Kriwacki, R., Parker, M., Gupta, P., Becksfort, J., Wei, L., Mulder, H.L., Boggs, K., Vadodaria, B., Yergeau, D., Russell, J.C., Ochoa, K., Fulton, R.S., Fulton, L.L., Jones, C., Boop, F.A., Broniscer, A., Wetmore, C., Gajjar, A., Ding, L., Mardis, E.R., Wilson, R.K., Taylor, M.R., Downing, J.R., Ellison, D.W., Zhang, J., Baker, S.J. and St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome, P. (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat. Genet. 46, 444-450
149. Yorukoglu, D., Hach, F., Swanson, L., Collins, C.C., Birol, I. and Sahinalp, S.C. (2012) Dissect: Detection and characterization of novel structural alterations in transcribed sequences. Bioinformatics 28, i179-187
150. Yoshida, A., Shibata, T., Tsuta, K., Watanabe, S. and Tsuda, H. (2013) Inflammatory myofibroblastic tumour of the lung with a novel PPFIBP1-ALK fusion variant. Histopathology 63, 881-883
151. Zabriskie, M.S., Eide, C.A., Tantravahi, S.K., Vellore, N.A., Estrada, J., Nicolini, F.E., Khoury, H.J., Larson, R.A., Konopleva, M., Cortes, J.E., Kantarjian, H., Jabbour, E.J., Kornblau, S.M., Lipton, J.H., Rea, D., Stenke, L., Barbany, G., Lange, T., Hernandez-Boluda, J.C., Ossenkoppele, G.J., Press, R.D., Chuah, C., Goldberg, S.L., Wetzler, M., Mahon, F.X., Etienne, G., Baccarani, M., Soverini, S., Rosti, G., Rousselot, P., Friedman, R., Deininger, M., Reynolds, K.R., Heaton, W.L., Eiring, A.M., Pomicter, A.D., Khorashad, J.S., Kelley, T.W., Baron, R., Druker, B.J., Deininger, M.W. and O'Hare, T. (2014) BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell 26, 428-442
152. Zhang, J., Wu, G., Miller, C.P., Tatevossian, R.G., Dalton, J.D., Tang, B., Orisme, W., Punchihewa, C., Parker, M., Qaddoumi, I., Boop, F.A., Lu, C., Kandoth, C., Ding, L., Lee, R., Huether, R., Chen, X., Hedlund, E., Nagahawatte, P., Rusch, M., Boggs, K., Cheng, J., Becksfort, J., Ma, J., Song, G., Li, Y., Wei, L., Wang, J., Shurtleff, S., Easton, J., Zhao, D., Fulton, R.S., Fulton, L.L., Dooling, D.J., Vadodaria, B., Mulder, H.L., Tang, C., Ochoa, K., Mullighan, C.G., Gajjar, A., Kriwacki, R., Sheer, D., Gilbertson, R.J., Mardis, E.R., Wilson, R.K., Downing, J.R., Baker, S.J., Ellison, D.W. and St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome, P. (2013) Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet. 45, 602-612