Cancer Immunity, Vol. 8, p. 11 (27 June 2008) Submitted: 29 February 2008. Accepted: 21 May 2008.
Pedro M. S. Alves1*, Nicole Lévy2*, Brian J. Stevenson3*, Hanifa Bouzourene4, Grégory Theiler3, Gabriel Bricard5, Sebastien Viatte1,2, Maha Ayyoub5, Henri Vuilleumier6, Jean-Claude R. Givel6, Donata Rimoldi2, Daniel E. Speiser5, C. Victor Jongeneel3, Pedro J. Romero1,5 and Frédéric Lévy1,2**
1National Center of Competence in Research (NCCR), Molecular Oncology, ISREC, Ch. des Boveresses 155, 1066 Epalinges, Switzerland
2Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland
3Ludwig Institute for Cancer Research and Swiss Institute of Bioinformatics, Génopode, 1015 Lausanne, Switzerland
4Institute of Pathology, University of Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland
5Ludwig Institute for Cancer Research, Division of Clinical Onco-Immunology, Av. Pierre-Decker 4, 1005 Lausanne, Switzerland
6Department of Visceral Surgery, University Hospital (CHUV), 1011 Lausanne, Switzerland
*These authors contributed equally to this work
**Present address: Debiopharm SA, Lausanne, Switzerland
Communicated by: LJ Old
Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitative RT-PCR on a cohort of colorectal cancer patients. From a pool of more than 6000 genes identified unambiguously in the analysis, we found 2124 genes that were selectively expressed in colon cancer tissue and 147 genes that were differentially expressed to a significant degree between normal and cancer cells. Differential expression of many genes was confirmed by RT-PCR on a cohort of patients. Despite the fact that deregulated genes were involved in many different cellular pathways, we found that genes expressed in the extracellular space were significantly over-represented in colorectal cancer. Strikingly, we identified a transcript from a chromosome X-linked member of the human endogenous retrovirus (HERV) H family that was frequently and selectively expressed in colon cancer but not in normal tissues. Our data suggest that this sequence should be considered as a target of immunological interventions against colorectal cancer.
Copyright © 2008 by Frédéric Lévy