1 Boveri, T. Zur Frage der Entstehung maligner Tumoren (Gustav Fischer, 1914).

2 Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).

3 Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546–1558 (2013).

4 Watson, I. R., Takahashi, K., Futreal, A. P. & Chin, L. Emerging patterns of somatic mutations in cancer. Nature Reviews Genet. 14, 703–718 (2013).

5 Mitelman, F., Johansson, B. & Mertens, F. Mitelman database of chromosome aberrations and gene fusions in cancer. National Cancer Institute [online], (2015).

6 Mitelman, F., Johansson, B. & Mertens, F. The impact of translocations and gene fusions on cancer causation. Nature Reviews Cancer 7, 233–245 (2007).

7 Nowell, P. C. & Hungerford, D. A. A minute chromosome in human chronic granulocytic leukemia. Science 132, 1497 (1960).

8 Caspersson, T., Zech, L. & Johansson, C. Differential binding of alkylating fluorochromes in human chromosomes. Exp. Cell Res. 60, 315–319 (1970).

9 Rowley, J. D. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290–293 (1973).

10 Rowley, J. D. Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann. Genet. 16, 109–112 (1973).

11 Zech, L., Haglund, U., Nilsson, K. & Klein, G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int. J. Cancer 17, 47–56 (1976).

12 Berger, R. et al. A new translocation in Burkitt's tumor cells. Hum. Genet. 53, 111–112 (1979).

13 Miyoshi, I., Hiraki, S., Kimura, I., Miyamoto, K. & Sato, J. 2/8 translocation in a Japanese Burkitt's lymphoma. Experientia 35, 742–743 (1979).

14 van den Berghe, H. et al. Variant translocation in Burkitt lymphoma. Cancer Genet. Cytogenet. 1, 9–14 (1979).

15 Oshimura, M., Freeman, A. I. & Sandberg, A. A. Chromosomes and causation of human cancer and leukemia. XXVI. Banding studies in acute lymphoblastic leukemia (ALL). Cancer 40, 1161–1172 (1977).

16 Rowley, J. D., Golomb, H. M. & Dougherty, C. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1, 549–550 (1977).

17 Fukuhara, S., Rowley, J. D., Variakojis, D. & Golomb, H. M. Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res. 39, 3119–3128 (1979).

18 Ohno, S. et al. Nonrandom chromosome changes involving the Ig gene-carrying chromosomes 12 and 6 in pristane-induced mouse plasmacytomas. Cell 18, 1001–1007 (1979).

19 Seidal, T., Mark, J., Hagmar, B. & Angervall, L. Alveolar rhabdomyosarcoma: a cytogenetic and correlated cytological and histological study. APMIS 90, 345–354 (1982).

20 Aurias, A., Rimbaut, C., Buffe, D., Dubousset, J. & Mazabraud, A. Chromosomal translocations in Ewing's sarcoma. N. Engl. J. Med. 309, 496–497 (1983).

21 Turc-Carel, C., Philip, I., Berger, M.-P., Philip, T. & Lenoir, G. M. Chromosomal translocations in Ewing's sarcoma. N. Engl. J. Med. 309, 497–498 (1983).

22 de Jong, B., Molenaar, I. M., Leeuw, J. A., Idenberg, V. J. S. & Oosterhuis, J. W. Cytogenetics of a renal adenocarcinoma in a 2-year-old child. Cancer Genet. Cytogenet. 21, 165–169 (1986).

23 Stenman, G., Sandros, J., Dahlenfors, R., Juberg-Ode, M. & Mark, J. 6q- and loss of the Y chromosome — two common deviations in malignant human salivary gland tumors. Cancer Genet. Cytogenet. 22, 283–293 (1986).

24 Mark, J., Dahlenfors, R., Ekedahl, C. & Stenman, G. The mixed salivary gland tumor — a normally benign human neoplasm frequently showing specific chromosomal abnormalities. Cancer Genet. Cytogenet. 2, 231–241 (1980).

25 Heim, S. et al. Reciprocal translocation t(3;12)(q27;q13) in lipoma. Cancer Genet. Cytogenet. 23, 301–304 (1986).

26 Turc-Carel, C., Dal Cin, P., Rao, U., Karakousis, C. & Sandberg, A. A. Cytogenetic studies of adipose tissue tumors. I. A benign lipoma with reciprocal translocation t(3;12)(q28;q14). Cancer Genet. Cytogenet. 23, 283–289 (1986).

27 Speicher, M. R. & Carter, N. P. The new cytogenetics: blurring the boundaries with molecular biology. Nature Reviews Genet. 6, 782–792 (2005).

28 Pinkel, D. & Albertson, D. G. Array comparative genomic hybridization and its application in cancer. Nature Genet. 37, S11–S17 (2005).

29 Wachtel, M. et al. Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1. Cancer Res. 64, 5539–5545 (2004).

30 Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644–648 (2005).

31 West, R. B. et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc. Natl Acad. Sci. USA 103, 690–695 (2006).

32 Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190–1203 (2007).

33 Soda, M. et al. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature 448, 561–566 (2007).

34 Wang, L. et al. Identification of a novel, recurrent HEY1–NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer 51, 127–139 (2012).

35 Bernard, O. et al. Two site-specific deletions and t(1;14) translocation restricted to human T-cell acute leukemias disrupt the 5′ part of the tal-1 gene. Oncogene 6, 1477–1488 (1991).

36 Barr, F. G. et al. In vivo amplification of the PAX3–FKHR and PAX7–FKHR fusion genes in alveolar rhabdomyosarcoma. Hum. Mol. Genet. 5, 15–21 (1996).

37 Simon, M.-P. et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nature Genet. 15, 95–98 (1997).

38 Sinclair, P. B. et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 95, 738–744 (2000).

39 Möller, E. et al. FUS–CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1. Clin. Cancer Res. 17, 2646–2656 (2011).

40 Gelsi-Boyer, V. et al. Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes. BMC Cancer 8, 299 (2008).

41 Van Vlierberghe, P. et al. The recurrent SET–NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia. Blood 111, 4668–4680 (2008).

42 Mullighan, C. G. et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nature Genet. 41, 1243–1246 (2009).

43 Santo, E. E. et al. Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma. Oncogene 31, 1571–1581 (2012).

44 Plaszczyca, A. et al. Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma. Int. J. Biochem. Cell. Biol. 53, 475–481 (2014).

45 Campbell, P. et al. Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nature Genet. 40, 722–729 (2008).

46 Maher, C. A. et al. Transcriptome sequencing to detect gene fusions in cancer. Nature 458, 97–101 (2009).

47 Maher, C. A. et al. Chimeric transcript discovery by paired-end transcriptome sequencing. Proc. Natl Acad. Sci. USA 106, 12353–12358 (2009).

48 Stephens, P. J. et al. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462, 1005–1010 (2009).

49 Hammerman, P. S. et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489, 519–525 (2012).

50 The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330–337 (2012).

51 Kandoth, C. et al. Integrated genomic characterization of endometrial carcinoma. Nature 497, 67–73 (2013).

52 Steidl, C. et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 471, 377–381 (2011).

53 Welch, J. S. et al. Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA 305, 1577–1584 (2011).

54 Roberts, K. G. et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell 22, 153–166 (2012).

55 Yoshihara, K. et al. The landscape and therapeutic relevance of cancer-associated transcript fusions. Oncogene http://dx.doi.org/10.1038/onc.2014.406 (2015).

56 The Cancer Genome Atlas Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059–2074 (2013).

57 The Cancer Genome Atlas Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499, 43–49 (2013).

58 The Cancer Genome Atlas Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507, 315–322 (2014).

59 The Cancer Genome Atlas Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543–550 (2014).

60 The Cancer Genome Atlas Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202–209 (2014).

61 Bass, A. J. et al. Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A–TCF7L2 fusion. Nature Genet. 43, 964–968 (2011).

62 Chmielecki, J. et al. Whole-exome sequencing identifies a recurrent NAB2–STAT6 fusion in solitary fibrous tumors. Nature Genet. 45, 131–132 (2013).

63 Mohajeri, A. et al. Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. Genes Chromosomes Cancer 52, 873–886 (2013).

64 Robinson, D. R. et al. Identification of recurrent NAB2–STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nature Genet. 45, 180–185 (2013).

65 Kalyana-Sundaram, S. et al. Gene fusions associated with recurrent amplicons represent a class of passenger aberrations in breast cancer. Neoplasia 14, 702–708 (2012).

66 Lou, D. I. et al. High-throughput DNA sequencing errors are reduced by orders of magnitude using circle sequencing. Proc. Natl Acad. Sci. USA 110, 19872–19877 (2013).

67 Sleep, J. A., Schreiber, A. W. & Baumann, U. Sequencing error correction without a reference genome. BMC Bioinformatics 14, 367 (2013).

68 Bourgon, R. et al. High-throughput detection of clinically relevant mutations in archived tumor samples by multiplexed PCR and next-generation sequencing. Clin. Cancer Res. 20, 2080–2091 (2014).

69 Shiroguchi, K., Jia, T. Z., Sims, P. A. & Xie, X. S. Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodes. Proc. Natl Acad. Sci. USA 109, 1347–1352 (2012).

70 Carrara, M. et al. State-of-the-art fusion-finder algorithms sensitivity and specificity. Biomed. Res. Int. 2013, 340620 (2013).

71 Hedegaard, J. et al. Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and formalin-fixed paraffin-embedded samples of human cancer and normal tissue. PLoS ONE 9, e98187 (2014).

72 Kim, D. & Salzberg, S. L. TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol. 12, R72 (2011).

73 Ozsolak, F. & Milos, P. M. RNA sequencing: advances, challenges and opportunities. Nature Reviews Genet. 12, 87–98 (2011).

74 Nacu, S. et al. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples. BMC Med. Genom. 4, 11 (2011).

75 Rickman, D. S. et al. SLC45A3–ELK4 is a novel and frequent erythroblast transformation-specific fusion transcript in prostate cancer. Cancer Res. 69, 2734–2738 (2009).

76 Gingeras, T. R. Implications of chimaeric non-co-linear transcripts. Nature 461, 206–211 (2009).

77 Zaphiropoulos, P. G. Trans-splicing in higher eukaryotes: implications for cancer development? Frontiers Genet. 2, 1–4 (2011).

78 Jividen, K. & Li, H. Chimeric RNAs generated by intergenic splicing in normal and cancer cells. Genes Chromosomes Cancer 53, 963–971 (2014).

79 Panagopoulos, I. Absence of the JAZF1/SUZ12 chimeric transcript in the immortalized non-neoplastic endometrial stromal cell line T HESCs. Oncol. Lett. 1, 947–950 (2010).

80 Hayward, W. S., Neel, B. G. & Astrin, S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature 290, 475–480 (1981).

81 Neel, B. G., Hayward, W. S., Robinson, H. L., Fang, J. & Astrin, S. M. Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion. Cell 23, 323–334 (1981).

82 Payne, G. S. et al. Analysis of avian leukosis virus DNA and RNA in bursal tumours: viral gene expression is not required for maintenance of the tumor state. Cell 23, 311–322 (1981).

83 Cairns, J. The origin of human cancers. Nature 289, 353–357 (1981).

84 Klein, G. The role of gene dosage and genetic transpositions in carcinogenesis. Nature 294, 313–318 (1981).

85 Leder, P. et al. Translocations among antibody genes in human cancer. Science 222, 765–771 (1983).

86 Croce, C. M. & Nowell, P. C. Molecular basis of neoplasia. Blood 65, 1–7 (1985).

87 Klein, G. & Klein, E. Conditioned tumorigenicity of activated oncogenes. Cancer Res. 46, 3211–3224 (1986).

88 Tsujimoto, Y. et al. Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science 224, 1403–1406 (1984).

89 Tsujimoto, Y., Finger, L. R., Yunis, J., Nowell, P. C. & Croce, C. M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226, 1097–1099 (1984).

90 Grimaldi, J. C. & Meeker, T. C. The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene. Blood 73, 2081–2085 (1989).

91 Korsmeyer, S. J. Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Annu. Rev. Immunol. 10, 785–807 (1992).

92 Erikson, J. et al. Deregulation of c-myc by translocation of the α-locus of the T-cell receptor in T-cell leukemias. Science 232, 884–886 (1986).

93 Hayashi, Y., Yamamoto, K. & Kojima, S. T-cell acute lymphoblastic leukemias with a t(8;14) possibly involving a c-myc locus and T-cell-receptor α-chain genes. N. Engl. J. Med. 314, 650–651 (1986).

94 Mathieu-Mahul, D. et al. A t(8;14)(q24;q11) translocation in a T-cell leukemia (L1-ALL) with c-myc and TcR-α chain locus rearrangements. Int. J. Cancer 38, 835–840 (1986).

95 McKeithan, T. W. et al. Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor α-chain gene and sequences on the 3′ side of MYC. Proc. Natl Acad. Sci. USA 83, 6636–6640 (1986).

96 Van Vlierberghe, P. & Ferrando, A. The molecular basis of T cell acute lymphoblastic leukemia. J. Clin. Invest. 122, 3398–3406 (2012).

97 Rabbitts, T. H. Chromosomal translocations in human cancer. Nature 372, 143–149 (1994).

98 O'Neil, J. & Look, A. T. Mechanisms of transcription factor deregulation in lymphoid cell transformation. Oncogene 26, 6838–6849 (2007).

99 Hatzi, K. & Melnick, A. Breaking bad in the germinal center: how deregulation of BCL6 contributes to lymphomagenesis. Trends Mol. Med. 20, 343–352 (2014).

100 Anderson, M. A., Huang, D. & Roberts, A. Targeting BCL2 for the treatment of lymphoid malignancies. Semin. Hematol. 51, 219–227 (2014).

101 Sonoki, T. et al. Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies. Blood 98, 2837–2844 (2001).

102 Clappier, E. et al. Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias. Leukemia 20, 82–86 (2006).

103 Hasanali, Z., Sharma, K. & Epner, E. Flipping the cyclin D1 switch in mantle cell lymphoma. Best Pract. Res. Clin. Haematol. 25, 143–152 (2012).

104 Russell, L. J. et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 114, 2688–2698 (2009).

105 Karrman, K. et al. The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor β locus. Br. J. Haematol. 144, 546–551 (2009).

106 Nagel, I. et al. Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies. Blood 116, 1317–1320 (2010).

107 Kas, K. et al. Promoter swapping between the genes for a novel zinc finger protein and β-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations. Nature Genet. 15, 170–174 (1997).

108 Duhoux, F. P. et al. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies. Br. J. Haematol. 156, 76–88 (2012).

109 Oliveira, A. M. et al. Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 24, 3419–3426 (2005).

110 Shtivelman, E., Lifshitz, B., Gale, R. P. & Canaani, E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315, 550–554 (1985).

111 Stam, K. et al. Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome. N. Engl. J. Med. 313, 1429–1433 (1985).

112 Kamps, M. P., Murre, C., Sun, X. & Baltimore, D. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell 60, 547–555 (1990).

113 Nourse, J. et al. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60, 535–545 (1990).

114 von Lindern, M. et al. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek–can mRNA. Mol. Cell. Biol. 12, 1687–1697 (1992).

115 de Thé, H., Chomienne, C., Lanotte, M., Degos, L. & Dejean, A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus. Nature 347, 558–561 (1990).

116 Lemons, R. S. et al. Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia. Genes Chromosomes Cancer 2, 79–87 (1990).

117 Delattre, O. et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359, 162–165 (1992).

118 Pierotti, M. A. et al. Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC. Proc. Natl Acad. Sci. USA 89, 1616–1620 (1992).

119 Santoro, M. et al. Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype. J. Clin. Invest. 89, 1517–1522 (1992).

120 Crozat, A., Aman, P., Mandahl, N. & Ron, D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363, 640–644 (1993).

121 Sorensen, P. H. & Triche, T. J. Gene fusions encoding chimaeric transcription factors in solid tumours. Semin. Cancer Biol. 7, 3–14 (1996).

122 Barr, F. G. Chromosomal translocations involving paired box transcription factors in human cancer. Int. J. Biochem. Cell Biol. 29, 1449–1461 (1997).

123 Slape, C. & Aplan, P. D. The role of NUP98 gene fusions in hematologic malignancy. Leuk. Lymphoma 45, 1341–1350 (2004).

124 Krivtsov, A. V. & Armstrong, S. A. MLL translocations, histone modofactions and leukaemia stem-cell development. Nature Reviews Cancer 7, 823–833 (2007).

125 Meyer, C. et al. The MLL recombinome of acute leukemias in 2013. Leukemia 27, 2165–2176 (2013).

126 Seshagiri, S. et al. Recurrent R-spondin fusions in colon cancer. Nature 488, 660–664 (2012).

127 Frattini, V. et al. The integrated landscape of driver genomic alterations in glioblastoma. Nature Genet. 45, 1141–1149 (2013).

128 Duro, D. et al. Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9;14)(p21-22;q11) in an acute lymphoblastic leukemia of B-cell type. Cancer Res. 56, 848–854 (1996).

129 Storlazzi, C. T., Von Steyern, F. V., Domanski, H. A., Mandahl, N. & Mertens, F. Biallelic somatic inactivation of the NF1 gene through chromosomal translocations in a sporadic neurofibroma. Int. J. Cancer 117, 1055–1057 (2005).

130 Coyaud, E. et al. Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study. Blood 115, 3089–3097 (2010).

131 Ågerstam, H. et al. Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome. Genes Chromosomes Cancer 46, 635–643 (2007).

132 Büschges, R. et al. Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas. Brain Pathol. 9, 435–442 (1999).

133 Bohlander, S. K. ETV6: a versatile player in leukemogenesis. Semin. Cancer. Biol. 15, 162–174 (2005).

134 Clappier, E. et al. The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children. Blood 110, 1251–1261 (2007).

135 Mullighan, C. G. et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446, 758–764 (2007).

136 Tzoneva, G. & Ferrando, A. A. Recent advances on NOTCH signaling in T-ALL. Curr. Top. Microbiol. Immunol. 360, 163–182 (2012).

137 Huether, R. et al. The landscape of somatic mutations in epigenetic regulators across 1,000 pediatric cancer genomes. Nature Commun. 5, 3630 (2014).

138 Hofvander, J. et al. Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma. Clin. Cancer Res. 21, 864–869 (2015).

139 Tomlins, S. A. et al. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci. Transl. Med. 3, 94ra72 (2011).

140 Balgobind, B. V. et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 114, 2489–2496 (2009).

141 Williamson, D. et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J. Clin. Oncol. 28, 2151–2158 (2010).

142 Doyle, L. A. et al. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am. J. Surg. Pathol. 35, 733–741 (2011).

143 Minca, E. C. et al. ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH. J. Mol. Diagn. 15, 341–346 (2013).

144 Shah, R. B. Clinical applications of novel ERG immunohistochemistry in prostate cancer diagnosis and management. Adv. Anat. Pathol. 20, 117–124 (2013).

145 Doyle, L. A. et al. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod. Pathol. 27, 390–395 (2014).

146 Swerdlow, S. H. et al. (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (IARC, 2008).

147 Fletcher, C. D. M., Bridge, J. A., Hogendoorn, P. C. W. & Mertens, F. (eds) WHO Classification of Tumours of Soft Tissue and Bone (IARC, 2013).

148 Hokland, P. & Ommen, H. B. Towards individualized follow-up in adult acute myeloid leukemia in remission. Blood 117, 2577–2584 (2011).

149 Crowley, E., Di Nicolantonio, F., Loupakis, F. & Bardelli, A. Liquid biopsy: monitoring cancer-genetics in the blood. Nature Reviews Clin. Oncol. 10, 472–484 (2013).

150 Karabacak, N. M. et al. Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nature Protoc. 9, 694–710 (2014).

151 Watanabe, M. et al. A novel flow cytometry-based cell capture platform for the detection, capture and molecular characterization of rare tumor cells in blood. J. Transl. Med. 12, 143 (2014).

152 Yu, K. H. et al. Pharmacogenomic modeling of circulting and invasive cells for prediction of chemotherapy response and resistance in pancreatic cancer. Clin. Cancer Res. 20, 5281–5289 (2014).

153 Leary, R. J. et al. Development of personalized tumor biomarkers using massively parallel sequencing. Sci. Transl. Med. 2, 20ra14 (2010).

154 Druker, B. J. Translation of the Philadelphia chromosome into therapy for CML. Blood 112, 4808–4817 (2008).

155 Rutkowski, P. et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two Phase II clinical trials. J. Clin. Oncol. 28, 1772–1779 (2010).

156 Lee, H. J., Thompson, J. E., Wang, E. S. & Wetzler, M. Philadelphia chromosome-positive acute lymphoblastic leukemia: current treatment and future perspectives. Cancer 117, 1583–1594 (2011).

157 Joensuu, H. Adjuvant treatment of GIST: patient selection and treatment strategies. Nature Reviews Clin. Oncol. 9, 351–358 (2012).

158 Kohno, T. et al. RET fusion gene: translation to personalized lung cancer therapy. Cancer Sci. 104, 1396–1400 (2013).

159 Shaw, A. T. et al. Tyrosine kinase gene rearrangements in epithelial malignancies. Nature Reviews Cancer 13, 772–787 (2013).

160 Feng, F. Y., Brenner, J. C., Hussain, M. & Chinnaiyan, A. M. Molecular pathways: targeting ETS gene fusions in cancer. Clin. Cancer Res. 20, 4442–4448 (2014).

161 Parker, B. C., Engels, M., Annala, M. & Zhang, W. Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours. J. Pathol. 232, 4–15 (2014).

162 Højfeldt, J. W., Agger, K. & Helin, K. Histone lysine demethylases as targets for anticancer therapy. Nature Reviews Drug Discov. 12, 917–930 (2013).

163 Sanger, F. et al. Nucleotide sequence of bacteriophage Φ X174 DNA. Nature 265, 687–695 (1977).

164 Sanger, F., Nicklen, S. & Coulson, A. R. DNA sequencing with chain-terminating inhibitors. Proc. Natl Acad. Sci. USA 74, 5463–5467 (1977).

165 Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376–380 (2005).

166 Shendure, J. et al. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309, 1728–1732 (2005).

167 Volik, S. et al. End-sequence profiling: sequence-based analysis of aberrant genomes. Proc. Natl Acad. Sci. USA 100, 7696–7701 (2003).

168 Volik, S. et al. Decoding the fine-scale structure of a breast cancer genome and transcriptome. Genome Res. 16, 394–404 (2006).

169 Ng, P. et al. Gene identification signature (GIS) analysis for transcriptome characterization and genomic annotation. Nature Methods 2, 105–111 (2005).

170 Ng, P. et al. Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Res. 34, e84 (2006).

171 Korbel, J. O. et al. Paired-end mapping reveals extensive structural variation in the human genome. Science 318, 420–426 (2007).