The Gene Associated with Trichorhinophalangeal Syndrome in Humans Is Overexpressed in Breast Cancer

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-08, Vol.102 (31), p.11005-11010
• Main Authors: Radvanyi, Laszlo, Singh-Sandhu, Devender, Gallichan, Scott, Lovitt, Corey, Pedyczak, Artur, Mallo, Gustavo, Gish, Kurt, Kwok, Kevin, Hanna, Wedad, Zubovits, Judith, Armes, Jane, Venter, Deon, Hakimi, Jalil, Shortreed, Jean, Donovan, Melinda, Parrington, Mark, Dunn, Pamela, Oomen, Ray, Tartaglia, James, Berinstein, Neil L., Mak, Tak Wah
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Biological Sciences; Breast cancer; Breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell lines; DNA, Neoplasm - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epitopes - genetics; Epitopes - metabolism; Female; Gene expression; Gene Expression Profiling; Genes; Humans; Immunohistochemistry; Langer-Giedion Syndrome - genetics; Medical disorders; Medical research; Mice; Mice, Transgenic; Molecular Sequence Data; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Noninfiltrating intraductal carcinoma; Oligonucleotide Array Sequence Analysis; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; T lymphocytes; T-Lymphocytes - immunology; Tissue samples; Transcription Factors; Tumor cell line; Tumors; Vaccination
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0500904102

A comprehensive differential gene expression screen on a panel of 54 breast tumors and >200 normal tissue samples using DNA microarrays revealed 15 genes specifically overexpressed in breast cancer. One of the most prevalent genes found was trichorhinophalangeal syndrome type 1 (TRPS-1), a gene previously shown to be associated with three rare autosomal dominant genetic disorders known as the trichorhinophalangeal syndromes. A number of corroborating methodologies, including in situ hybridization, e-Northern analysis using ORF EST (ORESTES) and Unigene EST abundance analysis, immunoblot and immunofluorescence analysis of breast tumor cell lines, and immunohistochemistry, confirmed the microarray findings. Immunohistochemistry analysis found TRPS-1 protein expressed in >90% of early- and late-stage breast cancer, including ductal carcinoma in situ and invasive ductal, lobular, and papillary carcinomas. The TRPS-1 gene is also immunogenic with processed and presented peptides activating T cells found after vaccination of HLA-A2.1 transgenic mouse. Human T cell lines from HLA- A*0201+female donors exhibiting TRPS-1-specific cytotoxic T lymphocyte activity could also be generated.