Recurrent gene fusions in prostate cancer

Nature Reviews Cancer

Volumn 8, Issue 7, 2008, Pages 497-511

  Kumar Sinha, Chandan ^a   Tomlins, Scott A ^a   Chinnaiyan, Arul M ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ANTIANDROGEN; BICALUTAMIDE; CYPROTERONE; CYPROTERONE ACETATE; ESTROGEN; FLUTAMIDE; GONADORELIN AGONIST; TRANSCRIPTION FACTOR ERG; TRANSCRIPTION FACTOR ETS;

BIOINFORMATICS; CANCER DIAGNOSIS; CANCER MORPHOLOGY; CANCER SCREENING; CARCINOGENESIS; CASTRATION; CHROMOSOME REARRANGEMENT; CLINICAL FEATURE; DNA FLANKING REGION; EPITHELIUM TUMOR; FUSION GENE; GENE FREQUENCY; GENE FUSION; GENE OVEREXPRESSION; GENETIC VARIABILITY; HEMATOLOGIC MALIGNANCY; HISTOPATHOLOGY; HUMAN; METASTASIS; MOLECULAR BIOLOGY; MULTIPLE CANCER; PRIORITY JOURNAL; PROGNOSIS; PROSTATE CANCER; REVIEW; SARCOMA; TMPRSS2 GENE;

COMPUTATIONAL BIOLOGY; GENE FUSION; HUMANS; MALE; PROSTATIC NEOPLASMS;

EID: 45849103492     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc2402     Document Type: Review

References (124)

1. American Cancer Society: Cancer Facts & Figures 2007 [online] http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf (2007).
2. Lilja, H., Ulmert, D. & Vickers, A. J. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nature Rev. Cancer 8, 268-278 (2008).
3. Denmeade, S. R. & Isaacs, J. T. A history of prostate cancer treatment. Nature Rev. Cancer 2, 389-396 (2002).
4. Loeb, S. & Catalona, W. J. Prostate-specific antigen in clinical practice. Cancer Lett. 249, 30-39 (2007).
5. Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644-648 (2005). This manuscript reported the discovery of recurrent gene fusions in a majority of prostate cancers.
6. Futreal, P. A. et al. A census of human cancer genes. Nature Rev. Cancer 4, 177-183 (2004).
7. Ren, R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nature Rev. Cancer 5, 172-183 (2005).
8. Goldman, J. M. & Melo, J. V. Chronic myeloid leukemia - advances in biology and new approaches to treatment. N. Engl. J. Med. 349, 1451-1464 (2003).
9. Nowell, P. C. & Hungerford, D. A. Chromosome studies on normal and leukemic human leukocytes. J. Natl Cancer Inst. 25, 85-109 (1960).
10. Nowell, P. C. & Hungerford, D. A. Chromosome studies in human leukemia. II. Chronic granulocytic leukemia. J. Natl Cancer Inst. 27, 1013-1035 (1961). References 9 & 10 were the first reports of the association between a chromosomal aberration (Philadelphia chromosome) and a malignancy (CML).
11. Rowley, J. D. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290-293 (1973).
12. Rowley, J. D. Chromosome translocations: dangerous liaisons revisited. Nature Rev. Cancer 1, 245-250 (2001).
13. Druker, B. J. et al. 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. 344, 1038-1042 (2001).
14. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037 (2001). References 13 and 14 established Gleevec/imatinib as a specific inhibitor of BCR-ABL1 in CML.
15. Mitelman, F., Mertens, F. & Johansson, B. Prevalence estimates of recurrent balanced cytogenetic aberrations and gene fusions in unselected patients with neoplastic disorders. Genes Chromosomes Cancer 43, 350-366 (2005).
16. Kumar-Sinha, C., Tomlins, S. A. & Chinnaiyan, A. M. Evidence of recurrent gene fusions in common epithelial tumors. Trends Mol. Med. (2006).
17. Mitelman, F. Recurrent chromosome aberrations in cancer. Mutat. Res. 462, 247-253 (2000).
18. Mitelman, F., Johansson, B., Mandahl, N. & Mertens, F. Clinical significance of cytogenetic findings in solid tumors. Cancer Genet. Cytogenet. 95, 1-8 (1997).
19. Mitelman, F., Johansson, B. & Mertens, F. Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nature Genet. 36, 331-334 (2004). Based on an analysis of prevalence of gene fusions across all cancer types, the authors observed: "Our results support the unorthodox concept that cytogenetic aberrations resulting in deregulated or rearranged genes may be of greater importance as an initial step in epithelial tumorigenesis than generally believed."
20. Narod, S. A. & Foulkes, W. D. BRCA1 and BRCA2: 1994 and beyond. Nature Rev. Cancer 4, 665-676 (2004).
21. Jeter, J. M., Kohlmann, W. & Gruber, S. B. Genetics of colorectal cancer. Oncology (Williston Park) 20, 269-276; discussion 285-286, 288-289 (2006).
22. Rowley, P. T. Inherited susceptibility to colorectal cancer. Annu. Rev. Med. 56, 539-554 (2005).
23. Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129-2139 (2004).
24. Rhodes, D. R. et al. Molecular concepts analysis links tumors, pathways, mechanisms, and drugs. Neoplasia 9, 443-454 (2007).
25. Rhodes, D. R. et al. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia 9, 166-180 (2007).
26. Rhodes, D. R. et al. Mining for regulatory programs in the cancer transcriptome. Nature Genet. 37, 579-583 (2005).
27. Rhodes, D. R. et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6, 1-6 (2004).
28. Oikawa, T. & Yamada, T. Molecular biology of the Ets family of transcription factors. Gene 303, 11-34 (2003).
29. Sorensen, P. H. et al. A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nature Genet. 6, 146-151 (1994).
30. Adams, J. M. et al. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318, 533-538 (1985).
31. Taub, R. et al. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc. Natl Acad. Sci. USA 79, 7837-7841 (1982).
32. 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).
33. Tomlins, S. A. et al. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 448, 595-599 (2007). This paper reported four novel classes of Ets gene fusions in prostate cancer, besides TMPRSS2, indicating a complex texture of gene fusions in solid cancers
34. Tomlins, S. A. et al. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 66, 3396-3400 (2006).
35. Helgeson, B. E. et al. Characterization of TMPRSS2: ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer. Cancer Res. 68, 73-80 (2008).
36. Hermans, K. G. et al. Two unique novel prostate-specific and androgen-regulated fusion partners of ETV4 in prostate cancer. Cancer Res. 68, 3094-3098 (2008).
37. MacDonald, J. W. & Ghosh, D. COPA - cancer outlier profile analysis. Bioinformatics 22, 2950-2951 (2006).
38. Tibshirani, R. & Hastie, T. Outlier sums for differential gene expression analysis. Biostatistics 8, 2-8 (2007).
39. Annunziata, C. M. et al. Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 12, 115-130 (2007).
40. Demichelis, F. et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 26, 4596-4599 (2007).
41. Cerveira, N. et al. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia 8, 826-832 (2006).
42. Clark, J. et al. Diversity of TMPRSS2-ERG fusion transcripts in the human prostate. Oncogene 26, 2667-2673 (2007).
43. Perner, S. et al. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res. 66, 8337-8341 (2006).
44. Perner, S. et al. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am. J. Surg. Pathol. 31, 882-888 (2007).
45. Mehra, R. et al. Characterization of TMPRSS2-ETS gene aberrations in androgen-independent metastatic prostate cancer. Cancer Res. 68, 3584-3590 (2008).
46. Hermans, K. G. et al. TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. Cancer Res. 66, 10658-10663 (2006).
47. Iljin, K. et al. TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. Cancer Res. 66, 10242-10246 (2006).
48. Lapointe, J. et al. A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. Mod. Pathol. 20, 467-473 (2007).
49. Rajput, A. B. et al. Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers. J. Clin. Pathol. 60, 1238-1243 (2007).
50. Soller, M. J. et al. Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer. Genes Chromosomes Cancer 45, 717-719 (2006).
51. Yoshimoto, M. et al. Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement. Neoplasia 8, 465-469 (2006).
52. Wang, J., Cai, Y., Ren, C. & Ittmann, M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res. 66, 8347-8351 (2006).
53. Liu, W. et al. Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancers. Genes Chromosomes Cancer 46, 972-980 (2007).
54. Melo, J. V. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 88, 2375-2384 (1996).
55. Lynch, H. T., Smyrk, T. & Lynch, J. F. Overview of natural history, pathology, molecular genetics and management of HNPCC (Lynch Syndrome). Int. J. Cancer 69, 38-43 (1996).
56. Halvarsson, B. et al. Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression. J. Clin. Pathol. 60, 781-786 (2007).
57. Lakhani, S. R. et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J. Natl Cancer Inst. 90, 1138-1145 (1998).
58. Lakhani, S. R. The pathology of familial breast cancer: Morphological aspects. Breast Cancer Res. 1, 31-35 (1999).
59. Mosquera, J. M. et al. Morphological features of TMPRSS2-ERG gene fusion prostate cancer. J. Pathol. 212, 91-101 (2007).
60. Tu, J. J. et al. Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues. Mod. Pathol. 20, 921-928 (2007).
61. Mehra, R. et al. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod. Pathol. 20, 538-544 (2007).
62. Nami, R. K. et al. Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression. Cancer Biol. Ther. 6, 40-45 (2007).
63. Nam, R. K. et al. Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br. J. Cancer 97, 1690-1695 (2007).
64. Attard, G. et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene 27, 253-263 (2007). This paper analysed the prognosis of prostate cancer patients with respect to their TMPRSS2-ERG rearrangement status and concluded that duplication of the fusion is associated with very poor cause-specific survival (25% survival at 8 years) compared with ERG rearrangement-negative cases (90% survival at 8 years).
65. Petrovics, G. et al. Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome. Oncogene 24, 3847-3852 (2005).
66. Winnes, M., Lissbrant, E., Damber, J. E. & Stenman, G. Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer. Oncol. Rep. 17, 1033-1036 (2007).
67. Arora, R. et al. Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate. Cancer 100, 2362-2366 (2004).
68. Mehra, R. et al. Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res. 67, 7991-7995 (2007).
69. Barry, M., Perner, S., Demichelis, F. & Rubin, M. A. TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications. Urology 70, 630-633 (2007).
70. Clark, J. et al. Complex patterns of ETS gene alteration arise during cancer development in the human prostate. Oncogene 27, 1993-2003 (2008).
71. Mehra, R. et al. Characterization of TMPRSS2-ETS gene aberrations in androgen independent metastatic prostate cancer. Cancer Res. 68, 3584-3590 (2008).
72. Skoda, R. & Prchal, J. T. Lessons from familial myeloproliferative disorders. Semin. Hematol. 42, 266-273 (2005).
73. Langeberg, W. J., Isaacs, W. B. & Stanford, J. L. Genetic etiology of hereditary prostate cancer. Front. Biosci. 12, 4101-4110 (2007).
74. Setlur, S. R. et al. Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer. J. Natl Cancer Inst.100, 915-925 (2008).
75. Bonkhoff, H., Fixemer, T., Hunsicker, I. & Remberger, K. Estrogen receptor expression in prostate cancer and premalignant prostatic lesions. Am. J. Pathol. 155, 641-647 (1999).
76. Glinsky, G. V., Glinskii, A. B., Stephenson, A. J., Hoffman, R. M. & Gerald, W. L. Gene expression profiling predicts clinical outcome of prostate cancer. J. Clin. Invest. 113, 913-923 (2004).
77. Tomlins, S. A. et al. Integrative molecular concept modeling of prostate cancer progression. Nature Genet. 39, 41-51 (2007).
78. Lapointe, J. et al. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc. Natl Acad. Sci. USA 101, 811-816 (2004).
79. Kim, J. H. et al. Integrative analysis of genomic aberrations associated with prostate cancer progression. Cancer Res. 67, 8229-8239 (2007).
80. Lapointe, J. et al. Genomic profiling reveals alternative genetic pathways of prostate tumorigenesis. Cancer Res. 67, 8504-8510 (2007).
81. Lin, B. et al. Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 59, 4180-4184 (1999).
82. Afar, D. E. et al. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res. 61, 1686-1692 (2001).
83. Vaarala, M. H., Porvari, K., Kyllonen, A., Lukkarinen, O. & Vihko, P. The TMPRSS2 gene encoding transmembrane serine protease is overexpressed in a majority of prostate cancer patients: detection of mutated TMPRSS2 form in a case of aggressive disease. Int. J. Cancer 94, 705-710 (2001).
84. Mertz, K. D. et al. Molecular characterization of TMPRSS2-ERG gene fusion in the NCI-H660 prostate cancer cell line: a new perspective for an old model. Neoplasia 9, 200-206 (2007).
85. Cai, C. et al. ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion. Mol. Endocrinol. 21, 1835-1846 (2007).
86. Ellwood-Yen, K. et al. Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell 4, 223-238 (2003).
87. Tomlins, S. A. et al. Role of the TMPRSS2-ERG gene fusion in prostate cancer. Neoplasia 10, 177-188 (2008).
88. Klezovitch, O. et al. A causal role for ERG in neoplastic transformation of prostate epithelium. Proc. Natl Acad. Sci. USA 105, 2105-2110 (2008).
89. Klezovitch, O. et al. A causal role for ERG in neoplastic transformation of prostate epithelium. Proc. Natl Acad. Sci USA 105, 2105-2110 (2008).
90. Shaffer, D. R. & Pandolfi, P. P. Breaking the rules of cancer. Nature Med. 12, 14-15 (2006).
91. Crawford, E. D. PSA testing: what is the use? Lancet 365, 1447-1449
92. Stamey, T. A. et al. The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J. Urol. 172, 1297-1301 (2004).
93. Frankel, S., Smith, G. D., Donovan, J. & Neal, D. Screening for prostate cancer. Lancet 361, 1122-1128 (2003).
94. Mao, X. et al. Detection of TMPRSS2:ERG fusion gene in circulating prostate cancer cells. Asian J. Androl. 10, 467-473 (2008).
95. Laxman, B. et al. Noninvasive detection of TMPRSS2: ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 8, 885-888 (2006).
96. Laxman, B. et al. A first generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res. 68, 645-649 (2007).
97. Hessels, D. et al. 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 (2007).
98. Huggins, C. & Hodges, C. V. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1, 5 (1941).
99. Huggins, C., Stevens, R. E. & Hodges, C. V. Studies on prostatic cancer: 2. The effects of castration on advanced carcinoma of the prostate gland. Arch. Surg. 43 209-222 (1941). References 98 and 99 mark the pioneering work of C. Huggins and C. V. Hodges that introduced androgen ablation therapy as a treatment modality for prostate cancer.
100. Schally, A. V., Kastin, A. J. & Arimura, A. Hypothalamic FSH and LH-regulating hormone. Structure, physiology and clinical studies. Fertil. Steril. 22, 703-721 (1971).
101. Denmeade, S. R. & Isaacs, J. T. in Cancer Medicine 5th edn (eds Bast, R. C. et al.) 765-776 (B. C. Decker, Hamilton, Ontario, 2000).
102. Steinberg, G. D. & Isaacs, J. T. in Cancer Chemotherapy (eds Hickman, J. A. & Hitton, T. R.) 322-341 (Blackwell Scientific Publications, Oxford, 1993).
103. Varenhorst, E., Wallentin, L. & Carlstrom, K. The effects of orchidectomy, estrogens, and cyproterone acetate on plasma testosterone, LH, and FSH concentrations in patients with carcinoma of the prostate. Scand. J. Urol. Nephrol. 16, 31-36 (1982).
104. Liao, S., Howell, D. K. & Chang, T. M. Action of a nonsteroidal antiandrogen, flutamide, on the receptor binding and nuclear retention of 5 α-dihydrotestosterone in rat ventral prostate. Endocrinology 94, 1205-1209 (1974).
105. Maximum androgen blockage in advanced prostate cancer: an overview of 22 randomised trials with 3283 deaths in 5710 patients. Lancet 346, 265-269 (1995).
106. Laufer, M., Denmeade, S. R., Sinibaldi, V., Carducci, M. & Eisenberger, M. A. Complete androgen blockade for prostate cancer: What went wrong? J. Urol. 164, 3-9 (2000).
107. Soda, M. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448, 561-566 (2007). The first report of a recurrent gene fusion in lung cancer.
108. Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 14 (2007).
109. Korbel, J. O. et al. Paired-end mapping reveals extensive structural variation in the human genome. Science 318, 420-426 (2007).
110. Ruan, Y. et al. Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs). Genome Res. 17, 828-838 (2007).
111. Rabbitts, T. H. Chromosomal translocations in human cancer. Nature 372, 143-149 (1994).
112. Gleissner, B. et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 99, 1536-1543 (2002).
113. Ribeiro, R. C. et al. Clinical and biologic hallmarks of the Philadelphia chromosome in childhood acute lymphoblastic leukemia. Blood 70, 948-953 (1987).
114. Nowell, P. C. & Hungerford, D. A. A minute chromosome in human chronic granulocytic leukemia. Science 132, 1497-1501 (1960).
115. Hughes, T. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108, 28-37 (2006).
116. Lugo, T. G., Pendergast, A. M., Muller, A. J. & Witte, O. N. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247, 1079-1082 (1990).
117. bcr/abl gene of the Philadelphia chromosome. Science 247, 824-830 (1990).
118. Elefanty, A. G., Hariharan, I. K. & Cory, S. bcr-abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice. EMBO J. 9, 1069-1078 (1990).
119. Kelliher, M. A., McLaughlin, J., Witte, O. N. & Rosenberg, N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc. Natl Acad. Sci. USA 87, 6649-6653 (1990).
120. Koschmieder, S. et al. Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis. Blood 105, 324-334 (2005).
121. Druker, B. J. et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355, 2408-2417 (2006).
122. Hughes, T. P. et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 349, 1423-1432 (2003).
123. O'Brien, S. G. et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 348, 994-1004 (2003).
124. Jhavar, S. et al. Detection of TMPRSS2-ERG translocations in human prostate cancer by expression profiling using GeneChip Human Exon 1.0 ST arrays. J. Mol. Diagn. 10, 50-57 (2008).