title: Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics.
abstract: BACKGROUND
  The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer.
  
  
  METHODS
  The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested.
  
  
  RESULTS
  BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by > 75% after infection with oncolytic viruses.
  
  
  CONCLUSIONS
  These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53 mutations. Although BIN-67 cells are resistant to standard chemotherapeutic agents, their sensitivity to oncolytic viruses suggests that their therapeutic use in SCCOHT should be considered.
authors: Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
authors: Lisa F
authors: LF
authors: Gamwell
authors: Karen
authors: K
authors: Gambaro
authors: Maria
authors: M
authors: Merziotis
authors: Colleen
authors: C
authors: Crane
authors: Suzanna L
authors: SL
authors: Arcand
authors: Valerie
authors: V
authors: Bourada
authors: Christopher
authors: C
authors: Davis
authors: Jeremy A
authors: JA
authors: Squire
authors: David G
authors: DG
authors: Huntsman
authors: Patricia N
authors: PN
authors: Tonin
authors: Barbara C
authors: BC
authors: Vanderhyden
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy; D002869:Chromosome Aberrations; D005260:Female; D020869:Gene Expression Profiling; D042822:Genomic Instability; D006801:Humans; D007621:Karyotyping; D051379:Mice; D009154:Mutation; D050130:Oncolytic Virotherapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents