title: Global expression analysis of cancer/testis genes in uterine cancers reveals a high incidence of BORIS expression.
abstract: OBJECTIVE
  Cancer/testis (CT) genes predominantly expressed in the testis (germ cells) and generally not in other normal tissues are aberrantly expressed in human cancers. This highly restricted expression provides a unique opportunity to use these CT genes for diagnostics, immunotherapeutic, or other targeted therapies. The purpose of this study was to identify those CT genes with the greatest incidence of expression in uterine cancers.
  
  
  METHODS
  We queried the expression of known and putative CT gene transcripts (representing 79 gene loci) using whole genome gene expression arrays. Specifically, the global gene expressions of uterine cancers (n = 122) and normal uteri (n = 10) were determined using expression data from the Affymetrix HG-U133A and HG-U133B chips. Additionally, we also examined the brother of the regulator of imprinted sites (BORIS) transcript by reverse transcription-PCR and quantitative PCR because its transcript was not represented on the array.
  
  
  RESULTS
  Global microarray analysis detected many CT genes expressed in various uterine cancers; however, no individual CT gene was expressed in more than 25% of all cancers. The expression of the two most commonly expressed CT genes on the arrays, MAGEA9 (24 of 122 cancers and 0 of 10 normal tissues) and Down syndrome critical region 8 (DSCR8)/MMA1 (16 if 122 cancers and 0 of 10 normal tissues), was confirmed by reverse transcription-PCR methods, validating the array screening approach. In contrast to the relatively low incidence of expression of the other CT genes, BORIS expression was detected in 73 of 95 (77%) endometrial cancers and 24 of 31 (77%) uterine mixed mesodermal tumors.
  
  
  CONCLUSIONS
  These data provide the first extensive survey of multiple CT genes in uterine cancers. Importantly, we detected a high frequency of BORIS expression in uterine cancers, suggesting its potential as an immunologic or diagnostic target for these cancers. Given the high incidence of BORIS expression and its possible regulatory role, an examination of BORIS function in the etiology of these cancers is warranted.
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. risin.Jo1@memorialhealth.com
authors.forename: John Ian
authors.initials: JI
authors.lastname: Risinger
authors.forename: Gadisetti V R
authors.initials: GV
authors.lastname: Chandramouli
authors.forename: G Larry
authors.initials: GL
authors.lastname: Maxwell
authors.forename: Mary
authors.initials: M
authors.lastname: Custer
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pack
authors.forename: Dmitri
authors.initials: D
authors.lastname: Loukinov
authors.forename: Olga
authors.initials: O
authors.lastname: Aprelikova
authors.forename: Tracy
authors.initials: T
authors.lastname: Litzi
authors.forename: David S
authors.initials: DS
authors.lastname: Schrump
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: J Carl
authors.initials: JC
authors.lastname: Barrett
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013737:Testis / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; C453740:DSCR8 lncRNA, human; C520253:MAGEA9 protein, human; D009363:Neoplasm Proteins