title: Molecular characterization of prostatic small-cell neuroendocrine carcinoma.
abstract: OBJECTIVE
  A subset of prostate carcinomas is composed predominantly, even exclusively, of neuroendocrine (NE) cells. In this report, we sought to characterize the gene expression profile of a prostate small cell NE carcinoma by assessing the diversity and abundance of transcripts in the LuCaP 49 prostate small cell carcinoma xenograft.
  
  
  METHODS
  We constructed a cDNA library (PRCA3) from the LuCap 49 prostate small cell xenograft. Single pass DNA sequencing of randomly selected cDNA clones followed by sequence assembly and annotation produced a library of Expressed Sequence Tags (ESTs) representing the LuCaP 49 transcriptome. Comparative sequence analysis with ESTs derived from prostate adenocarcinoma libraries was performed using statistical algorithms designed to identify differentially expressed sequences. Putative NE cell-specific genes were further examined by Northern analysis.
  
  
  RESULTS
  Sequence assembly and analysis identified 1,447 distinct genes expressed in the LuCaP 49 cDNA library. These include cDNAs encoding the NE markers secretogranin (SCG2), CD24, and ENO2. Northern analysis revealed that three additional genes, ASCL1, INA, and SV2B are expressed in LuCaP 49 but not in various prostate cancer cell lines or xenografts. Fifteen genes were identified with a statistical probability (P > 0.9) of being up-regulated in LuCaP 49 small cell carcinoma relative to prostate adenocarcinoma (two primary prostate adenocarcinomas and the LNCaP prostate adenocarcinoma cell line).
  
  
  CONCLUSIONS
  Prostate small cell carcinoma expresses a diverse repertoire of genes that reflect characteristics of their NE cell of origin. ASCL1, INA, and SV2B are potential molecular markers for small cell NE tumors and NE cells of the prostate. This small cell NE carcinoma gene expression profile may yield insights into the development, progression, and treatment of subtypes of prostate cancer.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, University of Washington-Seattle, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Clegg
authors.forename: Camari
authors.initials: C
authors.lastname: Ferguson
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.forename: Hugh
authors.initials: H
authors.lastname: Arnold
authors.forename: Alec
authors.initials: A
authors.lastname: Moorman
authors.forename: Janna E
authors.initials: JE
authors.lastname: Quinn
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000818:Animals; D015152:Blotting, Northern; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured