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* Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France;
INSERM, Unité 847, Montpellier, France;
Université Montpellier 1, Montpellier, France;
Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany; and
¶ Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany
Cancer-testis (CT) Ags are attractive targets for immunotherapeutic strategies since they are aberrantly expressed in malignant cells and not, or in limited number, in somatic tissues, except germ cells. To identify novel CT genes in multiple myeloma, we used Affymetrix HG-U133 gene expression profiles of 5 testis, 64 primary multiple myeloma cells (MMC), and 24 normal tissue samples. A 5-filter method was developed to keep known CT genes while deleting non-CT genes. Starting from 44,928 probe sets, including probe sets for 18 previously described CT genes, we have obtained 82 genes expressed in MMC and testis and not detected in more than 6 normal tissue samples. This list includes 14 of the 18 known CT genes and 68 novel putative CT genes. Real-time RT-PCR was performed for 34 genes in 12 normal tissue samples, 5 MMC samples, and one sample of five pooled testes. It has validated the CT status of 23 of 34 genes (67%). We found one novel "testis-restricted" gene (TEX14, expression in testis and tumor only), eight "tissue-restricted" (mRNA detected in one or two nongametogenic tissues), and seven "differentially expressed" (mRNA detected in three to six nongametogenic tissues) CT genes. Further studies are warranted to determine the immunogenicity of these novel CT Ag candidates.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Ligue Nationale Contre le Cancer (équipe labellisée 2009), Paris, France, from Institut National du Cancer (no. R07001FN), and from the Myeloma Stem Cell Network European Grant (no. E06005FF), the Hopp-Foundation, Germany, the University of Heidelberg, Heidelberg, Germany, the National Centre for Tumor Diseases, Heidelberg, Germany, and the Tumorzentrum Heidelberg/Mannheim, Germany.
M.C. designed research, performed the experiments, and wrote the paper; D.H., M.H., and H.G. collected bone marrow samples and clinical data; G.R. performed quantitative PCR experiments; T.R. developed bioinformatics tools to analyze the data; D.H. and M.H. participated in the writing of the paper; and B.K. is the senior investigator who designed research and wrote the paper.
2 Address correspondence and reprint requests to Dr. Bernard Klein, INSERM, Unité 847, Institute for Research in Biotherapy, Centre Hospitalier Universitaire Montpellier, Hospital St Eloi, Avenue Augustin Fliche, 34295 Montpellier, France. E-mail address: bernard.klein{at}inserm.fr
3 Abbreviations used in this paper: CT, cancer-testis; BMPC, bone marrow plasma cell; GEP, gene expression profiling; MBC, memory B cell; HMCL, human myeloma cell line; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; MMC, multiple myeloma cell; NT, normal tissue.
4 The online version of this article contains supplemental material.
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