Genome-wide analysis of cancer/testis gene expression.
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.
Hofmann
Oliver
O
Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, SPH2, 4th Floor, Boston, MA 02115, USA. ohofmann@hsph.harvard.edu
Caballero
Otavia L
OL
Stevenson
Brian J
BJ
Chen
Yao-Tseng
YT
Cohen
Tzeela
T
Chua
Ramon
R
Maher
Christopher A
CA
Panji
Sumir
S
Schaefer
Ulf
U
Kruger
Adele
A
Lehvaslaiho
Minna
M
Carninci
Piero
P
Hayashizaki
Yoshihide
Y
Jongeneel
C Victor
CV
Simpson
Andrew J G
AJ
Old
Lloyd J
LJ
Hide
Winston
W
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
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