An integrated approach of immunogenomics and bioinformatics to identify new Tumor Associated Antigens (TAA) for mammary cancer immunological prevention.
BACKGROUND
Neoplastic transformation is a multistep process in which distinct gene products of specific cell regulatory pathways are involved at each stage. Identification of overexpressed genes provides an unprecedented opportunity to address the immune system against antigens typical of defined stages of neoplastic transformation. HER-2/neu/ERBB2 (Her2) oncogene is a prototype of deregulated oncogenic protein kinase membrane receptors. Mice transgenic for rat Her2 (BALB-neuT mice) were studied to evaluate the stage in which vaccines can prevent the onset of Her2 driven mammary carcinomas. As Her2 is not overexpressed in all mammary carcinomas, definition of an additional set of tumor associated antigens (TAAs) expressed at defined stages by most breast carcinomas would allow a broader coverage of vaccination. To address this question, a meta-analysis was performed on two transcription profile studies to identify a set of new TAA targets to be used instead of or in conjunction with Her2.


RESULTS
The five TAAs identified (Tes, Rcn2, Rnf4, Cradd, Galnt3) are those whose expression is linearly related to the tumor mass increase in BALB-neuT mammary glands. Moreover, they have a low expression in normal tissues and are generally expressed in human breast tumors, though at a lower level than Her2.


CONCLUSIONS
Although the number of putative TAAs identified is limited, this pilot study suggests that meta-analysis of expression profiles produces results that could assist in the designing of pre-clinical immunopreventive vaccines.
Cavallo
Federica
F
Dept. of Clinical and Biological Sciences, University of Torino, Az. Ospedaliera S. Luigi, Regione Gonzole 10, I-10043 Orbassano, Italy. federica.cavallo@unito.it
Astolfi
Annalisa
A
Iezzi
Manuela
M
Cordero
Francesca
F
Lollini
Pier-Luigi
PL
Forni
Guido
G
Calogero
Raffaele
R
D000486:Allergy and Immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control*; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods*; D006801:Humans; D020407:Internet; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D015398:Signal Transduction
D000951:Antigens, Neoplasm; D004247:DNA