Ectopic expression of cancer-testis antigens in cutaneous T-cell lymphoma patients.
OBJECTIVE
The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains only partially understood. A number of recent studies attempted to identify novel diagnostic markers and future therapeutic targets. One group of antigens, cancer-testis (CT) antigens, normally present solely in testicular germ cells, can be ectopically expressed in a variety of cancers. Currently, only a few studies attempted to investigate the expression of CT antigens in CTCL.


METHODS
In the present work, we test the expression of CT genes in a cohort of patients with CTCL, normal skin samples, skin from benign inflammatory dermatoses, and in patient-derived CTCL cells. We correlate such expression with the p53 status and explore molecular mechanisms behind their ectopic expression in these cells.


RESULTS
Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11, and GTSF1 genes are heterogeneously expressed in patients with CTCL and patient-derived cell lines, whereas cTAGE1 (cutaneous T-cell lymphoma-associated antigen 1) was found to be robustly expressed in both. Mutated p53 status did not appear to be a requirement for the ectopic expression of CT antigens. While T-cell stimulation resulted in a significant upregulation of STAT3 and JUNB expression, it did not significantly alter the expression of CT antigens. Treatment of CTCL cells in vitro with vorinostat or romidepsin histone deacetylase inhibitors resulted in a significant dose-dependent upregulation of mRNA but not protein. Further expression analysis demonstrated that SYCP1, cTAGE1, and GTSF1 were expressed in CTCL, but not in normal skin or benign inflammatory dermatoses.


CONCLUSIONS
A number of CT genes are ectopically expressed in patients with CTCL and can be used as biomarkers or novel targets for immunotherapy.
Authors' Affiliations: Division of Dermatology, McGill University Health Centre, Montréal; denis.sasseville@mcgill.ca ivan.litvinov@mail.mcgill.ca.
Ivan V
IV
Litvinov
Authors' Affiliations: Division of Dermatology, McGill University Health Centre, Montréal;
Brendan
B
Cordeiro
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; and.
Yuanshen
Y
Huang
Authors' Affiliations: Division of Dermatology, McGill University Health Centre, Montréal;
Hanieh
H
Zargham
Authors' Affiliations: Division of Dermatology, McGill University Health Centre, Montréal;
Kevin
K
Pehr
Division of Dermatology, Université Laval, Québec;
Marc-André
MA
Doré
Division of Dermatology, Université Laval, Québec;
Martin
M
Gilbert
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada; and.
Youwen
Y
Zhou
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts.
Thomas S
TS
Kupper
Authors' Affiliations: Division of Dermatology, McGill University Health Centre, Montréal; denis.sasseville@mcgill.ca ivan.litvinov@mail.mcgill.ca.
Denis
D
Sasseville
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C063419:CTAGE1 protein, human; D004268:DNA-Binding Proteins; C575258:GTSF1 protein, human; D056572:Histone Deacetylase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011506:Proteins; C489753:SYCP1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53