Common gene rearrangements in prostate cancer.

Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease.

[1]  J. Cuzick,et al.  Complex patterns of ETS gene alteration arise during cancer development in the human prostate , 2008, Oncogene.

[2]  Arul M Chinnaiyan,et al.  TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. , 2006, Cancer research.

[3]  J. Damber,et al.  Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer. , 2007, Oncology reports.

[4]  Eric S. Lander,et al.  The genomic complexity of primary human prostate cancer , 2010, Nature.

[5]  L. Klotz,et al.  Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression , 2007, Cancer biology & therapy.

[6]  L. Liotta,et al.  Evidence of independent origin of multiple tumors from patients with prostate cancer. , 1998, Journal of the National Cancer Institute.

[7]  P. Nelson,et al.  A causal role for ERG in neoplastic transformation of prostate epithelium , 2008, Proceedings of the National Academy of Sciences.

[8]  Lang Li,et al.  Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate , 2004, Cancer.

[9]  M. Dowsett,et al.  Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). , 1994, The Journal of steroid biochemistry and molecular biology.

[10]  T. Tammela,et al.  TMPRSS2:ERG Fusion Identifies a Subgroup of Prostate Cancers with a Favorable Prognosis , 2008, Clinical Cancer Research.

[11]  M. Teitell,et al.  ETS family transcription factors collaborate with alternative signaling pathways to induce carcinoma from adult murine prostate cells , 2009, Proceedings of the National Academy of Sciences.

[12]  Jie Zhang,et al.  Nuclear Receptor-Induced Chromosomal Proximity and DNA Breaks Underlie Specific Translocations in Cancer , 2009, Cell.

[13]  David A Hanauer,et al.  Bioinformatics approaches in the study of cancer. , 2007, Current molecular medicine.

[14]  P. Scardino,et al.  A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. , 1991, The Journal of urology.

[15]  R. Eeles,et al.  Diversity of TMPRSS2-ERG fusion transcripts in the human prostate , 2007, Oncogene.

[16]  S. Dhanasekaran,et al.  A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer. , 2008, Cancer research.

[17]  Arul M Chinnaiyan,et al.  Bioinformatics approach leads to the discovery of the TMPRSS2:ETS gene fusion in prostate cancer , 2006, Laboratory Investigation.

[18]  O. Kallioniemi,et al.  TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. , 2006, Cancer research.

[19]  M. Rubin,et al.  Prevalence of TMPRSS2-ERG and SLC45A3-ERG gene fusions in a large prostatectomy cohort , 2009, Modern Pathology.

[20]  M. Rubin,et al.  SLC45A3-ELK4 is a novel and frequent erythroblast transformation-specific fusion transcript in prostate cancer. , 2009, Cancer research.

[21]  Yao-Tseng Chen,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 , 2007, Modern Pathology.

[22]  R. Henrique,et al.  TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. , 2006, Neoplasia.

[23]  R. Shah,et al.  Characterization of TMPRSS2-ETS gene aberrations in androgen-independent metastatic prostate cancer. , 2008, Cancer research.

[24]  A. Chinnaiyan,et al.  Triggers for genomic rearrangements: insights into genomic, cellular and environmental influences , 2011, Nature Reviews Genetics.

[25]  G. Jenster,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. , 2006, Cancer research.

[26]  D. Bostwick,et al.  Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization. , 1995, Cancer research.

[27]  B. Rubin,et al.  Mechanisms of resistance to small molecule kinase inhibition in the treatment of solid tumors , 2006, Laboratory Investigation.

[28]  Francesca Demichelis,et al.  Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma , 2010, Nature Medicine.

[29]  Adam S. Kibel,et al.  Integrative molecular concept modeling of prostate cancer progression , 2007 .

[30]  T. Golub,et al.  Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer. , 2008, Journal of the National Cancer Institute.

[31]  Martin J. Aryee,et al.  Androgen-induced TOP2B mediated double strand breaks and prostate cancer gene rearrangements , 2010, Nature Genetics.

[32]  M. Loda,et al.  Characterization of TMPRSS2-ERG Fusion High-Grade Prostatic Intraepithelial Neoplasia and Potential Clinical Implications , 2008, Clinical Cancer Research.

[33]  S. Varambally,et al.  Antibody-based detection of ERG rearrangement-positive prostate cancer. , 2010, Neoplasia.

[34]  S. Varambally,et al.  Therapeutic Targeting of SPINK1-Positive Prostate Cancer , 2011, Science Translational Medicine.

[35]  R. Tibshirani,et al.  Gene expression profiling identifies clinically relevant subtypes of prostate cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Lee T. Sam,et al.  Transcriptome Sequencing to Detect Gene Fusions in Cancer , 2009, Nature.

[37]  Jianfeng Xu,et al.  Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array , 2006, Genes, chromosomes & cancer.

[38]  D. Dearnaley,et al.  Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. , 2009, Cancer research.

[39]  J. Brooks,et al.  A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis , 2007, Modern Pathology.

[40]  J. Llovet,et al.  Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling , 2008, Molecular Cancer Therapeutics.

[41]  J. Witjes,et al.  Detection of TMPRSS2-ERG Fusion Transcripts and Prostate Cancer Antigen 3 in Urinary Sediments May Improve Diagnosis of Prostate Cancer , 2007, Clinical Cancer Research.

[42]  T. Guthrie,et al.  Prostate cancer. , 2020, American family physician.

[43]  Derek Y. Chiang,et al.  EML4-ALK Fusion Gene and Efficacy of an ALK Kinase Inhibitor in Lung Cancer , 2008, Clinical Cancer Research.

[44]  S. Leung,et al.  Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers , 2007, Journal of Clinical Pathology.

[45]  John T. Wei,et al.  The role of SPINK1 in ETS rearrangement-negative prostate cancers. , 2008, Cancer cell.

[46]  Lei Wang,et al.  Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. , 2006, Neoplasia.

[47]  B. Haynes,et al.  Pharmacology of novel steroidal inhibitors of cytochrome P45017α (17α-hydroxylase/C17–20 lyase) , 1994, The Journal of Steroid Biochemistry and Molecular Biology.

[48]  Michael Ittmann,et al.  Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. , 2006, Cancer research.

[49]  John F Ward,et al.  The long-term clinical impact of biochemical recurrence of prostate cancer 5 or more years after radical prostatectomy. , 2003, The Journal of urology.

[50]  D. Grignon,et al.  Allelic loss in locally metastatic, multisampled prostate cancer. , 1994, Cancer research.

[51]  D. Berney,et al.  Androgen-induced TMPRSS2:ERG fusion in nonmalignant prostate epithelial cells. , 2010, Cancer research.

[52]  C. Ahlers,et al.  ETS-TMPRSS2 fusion gene products in prostate cancer , 2006, Cancer biology & therapy.

[53]  M. Rubin,et al.  TMPRSS2-ERG Fusion Prostate Cancer: An Early Molecular Event Associated With Invasion , 2006, The American journal of surgical pathology.

[54]  I. Panagopoulos,et al.  Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer , 2006 .

[55]  Arul M Chinnaiyan,et al.  Prevalence of TMPRSS2-ERG Fusion Prostate Cancer among Men Undergoing Prostate Biopsy in the United States , 2009, Clinical Cancer Research.

[56]  J. Tchinda,et al.  TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. , 2006, Cancer research.

[57]  S. Varambally,et al.  Induced Chromosomal Proximity and Gene Fusions in Prostate Cancer , 2009, Science.

[58]  J Cuzick,et al.  Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer , 2008, Oncogene.

[59]  H. Aburatani,et al.  Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer , 2007, Nature.

[60]  T. Ratliff Prostate Pathology of Genetically Engineered Mice: Definitions and Classification. The Consensus Report From the Bar Harbor Meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee , 2004 .

[61]  M. Bissell A First-Generation Multiplex Biomarker Analysis of Urine For The Early Detection of Prostate Cancer , 2009 .

[62]  R. Shah,et al.  Role of the TMPRSS2-ERG gene fusion in prostate cancer. , 2008, Neoplasia.

[63]  P. Karakiewicz,et al.  25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series. , 2006, The Journal of urology.

[64]  Adam S. Kibel,et al.  TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort , 2007 .

[65]  A. Jemal,et al.  Cancer Statistics, 2010 , 2010, CA: a cancer journal for clinicians.

[66]  A. Evans,et al.  Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement. , 2006, Neoplasia.

[67]  M. Caligiuri,et al.  Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  P. Scardino,et al.  Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer. , 2006, The Journal of urology.

[69]  Ximing J. Yang,et al.  A Working Group Classification of Focal Prostate Atrophy Lesions , 2006, The American journal of surgical pathology.

[70]  Debashis Ghosh,et al.  Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer , 2007, Modern Pathology.

[71]  R. Shah,et al.  Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. , 2007, Cancer research.

[72]  C. Glass,et al.  A Topoisomerase IIß-Mediated dsDNA Break Required for Regulated Transcription , 2006, Science.

[73]  O. Ludkovski,et al.  Microdeletion and concurrent translocation associated with a complex TMPRSS2:ERG prostate cancer gene fusion , 2007, Genes, chromosomes & cancer.

[74]  J. Tchinda,et al.  Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. , 2006, Science.

[75]  A. Kibel The genomic complexity of primary human prostate cancer: Berger MF, Lawrence MS, Demichelis F, et al (The Broad Inst of Harvard and MIT, Cambridge, MA; Weill Cornell Med College, NY; et al) Nature 470:214-220, 2011 § , 2011 .

[76]  S. Dhanasekaran,et al.  Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer , 2007, Nature.

[77]  Mitch Dowsett,et al.  Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  S. Varambally,et al.  Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer. , 2008, Cancer research.

[79]  M. Rubin,et al.  TMPRSS2-ERG fusion heterogeneity in multifocal prostate cancer: clinical and biologic implications. , 2007, Urology.

[80]  M. Gerstein,et al.  N-myc downstream regulated gene 1 (NDRG1) is fused to ERG in prostate cancer. , 2009, Neoplasia.

[81]  S. Luo,et al.  Chimeric transcript discovery by paired-end transcriptome sequencing , 2009, Proceedings of the National Academy of Sciences.