Cancer Immunity 5:9 (2005)

Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein

Yao-Tseng Chen¹, Charis A. Venditti², Gregory Theiler³, Brian J. Stevenson³, Christian Iseli³, Ali O. Gure², C. Victor Jongeneel³, Lloyd J. Old², and Andrew J. G. Simpson²

¹Weill Medical College of Cornell University, New York, NY, USA
²Ludwig Institute for Cancer Research, New York Branch, New York, NY, USA
³Office of Information Technology, Ludwig Institute for Cancer Research, and Swiss Institute of Bioinformatics, Lausanne, Switzerland

Keywords: human, ESTs, cancer/testis, tumor antigens, HORMAD1, mRNA, tissue distribution

Abstract

Transcripts with ESTs derived exclusively or predominantly from testis, and not from other normal tissues, are likely to be products of genes with testis-restricted expression, and are thus potential cancer/testis (CT) antigen genes. A list of 371 genes with such characteristics was compiled by analyzing publicly available EST databases. RT-PCR analysis of normal and tumor tissues was performed to validate an initial selection of 20 of these genes. Several new CT and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed strongly in testis and weakly in placenta; the highest level of expression in other tissues is <1% of testicular expression. The CT46/HORMAD1 gene was expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing expression levels >10% of the testicular level of expression. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa. Conserved protein domain analysis identified a HORMA domain involved in chromatin binding. The CT46/HORMAD1 protein was found to be homologous to the prototype HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.