The gene associated with trichorhinophalangeal syndrome in humans is overexpressed in breast cancer.
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.
Radvanyi
Laszlo
L
Sanofi Pasteur, Toronto, Ontario, Canada M2R 3T4. lradvanyi@mdanderson.org
Singh-Sandhu
Devender
D
Gallichan
Scott
S
Lovitt
Corey
C
Pedyczak
Artur
A
Mallo
Gustavo
G
Gish
Kurt
K
Kwok
Kevin
K
Hanna
Wedad
W
Zubovits
Judith
J
Armes
Jane
J
Venter
Deon
D
Hakimi
Jalil
J
Shortreed
Jean
J
Donovan
Melinda
M
Parrington
Mark
M
Dunn
Pamela
P
Oomen
Ray
R
Tartaglia
James
J
Berinstein
Neil L
NL
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D015826:Langer-Giedion Syndrome / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors
D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000939:Epitopes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors