title: Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer.
abstract: 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.
authors.affiliation: National Center of Competence in Research, Molecular Oncology, ISREC, Ch. des Boveresses 155, 1066 Epalinges, Switzerland.
authors.forename: Pedro M S
authors.initials: PM
authors.lastname: Alves
authors.forename: Nicole
authors.initials: N
authors.lastname: Lévy
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: Hanifa
authors.initials: H
authors.lastname: Bouzourene
authors.forename: Grégory
authors.initials: G
authors.lastname: Theiler
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bricard
authors.forename: Sebastien
authors.initials: S
authors.lastname: Viatte
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Henri
authors.initials: H
authors.lastname: Vuilleumier
authors.forename: Jean-Claude R
authors.initials: JC
authors.lastname: Givel
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: C Victor
authors.initials: CV
authors.lastname: Jongeneel
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Romero
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lévy
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D020077:Endogenous Retroviruses / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C030139:colon-specific antigen