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Genome-wide analysis of cancer/testis gene expression.

Authors
  • Hofmann, Oliver1
  • Caballero, Otavia L
  • Stevenson, Brian J
  • Chen, Yao-Tseng
  • Cohen, Tzeela
  • Chua, Ramon
  • Maher, Christopher A
  • Panji, Sumir
  • Schaefer, Ulf
  • Kruger, Adele
  • Lehvaslaiho, Minna
  • Carninci, Piero
  • Hayashizaki, Yoshihide
  • Jongeneel, C Victor
  • Simpson, Andrew J G
  • Old, Lloyd J
  • Hide, Winston
  • 1 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, SPH2, 4th Floor, Boston, MA 02115, USA. [email protected]
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Dec 23, 2008
Volume
105
Issue
51
Pages
20422–20427
Identifiers
DOI: 10.1073/pnas.0810777105
PMID: 19088187
Source
Medline
Language
English
License
Unknown

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.

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