title: Genome-wide analysis of cancer/testis gene expression.
abstract: Cancer/Testis (CT) genes, normally expressed in germ line cells but also activated in a wide range of cancer types, often encode antigens that are immunogenic in cancer patients, and present potential for use as biomarkers and targets for immunotherapy. Using multiple in silico gene expression analysis technologies, including twice the number of expressed sequence tags used in previous studies, we have performed a comprehensive genome-wide survey of expression for a set of 153 previously described CT genes in normal and cancer expression libraries. We find that although they are generally highly expressed in testis, these genes exhibit heterogeneous gene expression profiles, allowing their classification into testis-restricted (39), testis/brain-restricted (14), and a testis-selective (85) group of genes that show additional expression in somatic tissues. The chromosomal distribution of these genes confirmed the previously observed dominance of X chromosome location, with CT-X genes being significantly more testis-restricted than non-X CT. Applying this core classification in a genome-wide survey we identified >30 CT candidate genes; 3 of them, PEPP-2, OTOA, and AKAP4, were confirmed as testis-restricted or testis-selective using RT-PCR, with variable expression frequencies observed in a panel of cancer cell lines. Our classification provides an objective ranking for potential CT genes, which is useful in guiding further identification and characterization of these potentially important diagnostic and therapeutic targets.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, SPH2, 4th Floor, Boston, MA 02115, USA. ohofmann@hsph.harvard.edu
authors.forename: Oliver
authors.initials: O
authors.lastname: Hofmann
authors.forename: Otavia L
authors.initials: OL
authors.lastname: Caballero
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Tzeela
authors.initials: T
authors.lastname: Cohen
authors.forename: Ramon
authors.initials: R
authors.lastname: Chua
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maher
authors.forename: Sumir
authors.initials: S
authors.lastname: Panji
authors.forename: Ulf
authors.initials: U
authors.lastname: Schaefer
authors.forename: Adele
authors.initials: A
authors.lastname: Kruger
authors.forename: Minna
authors.initials: M
authors.lastname: Lehvaslaiho
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: C Victor
authors.initials: CV
authors.lastname: Jongeneel
authors.forename: Andrew J G
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Winston
authors.initials: W
authors.lastname: Hide
mesh_terms: D054758:A Kinase Anchor Proteins; D045744:Cell Line, Tumor; D002877:Chromosomes, Human; D041321:Chromosomes, Human, X; D019295:Computational Biology; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics*; D013737:Testis
chemical_list: D054758:A Kinase Anchor Proteins; C485480:AKAP4 protein, human; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C456027:OTOA protein, human; C471968:RHOXF2 protein, human