title: Molecular biology underlying the clinical heterogeneity of prostate cancer: an update.
abstract: BACKGROUND
  Recent studies have uncovered a number of possible mechanisms by which prostate cancers can become resistant to systemic androgen deprivation, most involving androgen-independent reactivation of the androgen receptor. Genome-wide expression analysis with microarrays has identified a wide array of genes that are differentially expressed in metastatic prostate cancers compared to primary nonrecurrent tumors. Recently, recurrent gene fusions between TMPRSS2 and ETS family genes have been identified and extensively studied for their role in prostatic carcinoma.
  
  
  OBJECTIVE
  To review the recent developments in the molecular biology of prostate cancer, including those pertaining to the androgen receptor and the newly identified TMPRSS2-related translocations.
  
  
  METHODS
  Literature review and personal experience.
  
  
  CONCLUSIONS
  Prostatic adenocarcinoma is a heterogeneous group of neoplasms with a broad spectrum of pathologic and molecular characteristics and clinical behaviors. Numerous mechanisms contribute to the development of resistance to androgen ablation therapy, resulting in ligand-independent reactivation of the androgen receptor, including amplification, mutation, phosphorylation, and activation of coreceptors. Multiple translocations of members of the ETS oncogene family are present in approximately half of clinically localized prostate cancers. TMPRSS2:ERG gene rearrangement appears to be an early event in prostate cancer and is not observed in benign or hyperplastic prostatic epithelium. Duplication of TMPRSS2:ERG appears to predict a worse prognosis. The relationship between TMPRSS2:ERG gene rearrangement and other morphologic and prognostic parameters of prostate cancer is still unclear.
authors: Department of Pathology, University of Chicago, Chicago, Illinois, USA.
authors: A Craig
authors: AC
authors: Mackinnon
authors: Benjamin C
authors: BC
authors: Yan
authors: Loren J
authors: LJ
authors: Joseph
authors: Hikmat A
authors: HA
authors: Al-Ahmadie
mesh_terms: D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011944:Receptors, Androgen / Q000502:physiology; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D015514:Oncogene Proteins, Fusion; D011944:Receptors, Androgen; C515553:TMPRSS2-ERG fusion protein, human; C529660:TMPRSS2-ETS fusion protein, human