The Ectopic Expression of Meiosis Regulatory Genes in Cutaneous T-Cell Lymphomas (CTCL)

被引:15
|
作者
Gantchev, Jennifer [1 ]
Villarreal, Amelia Martinez [1 ]
Xie, Pingxing [1 ]
Lefrancois, Philippe [1 ]
Gunn, Scott [1 ]
Netchiporouk, Elena [1 ]
Sasseville, Denis [1 ]
Litvinov, Ivan V. [1 ]
机构
[1] McGill Univ, Div Dermatol, Montreal, PQ, Canada
来源
FRONTIERS IN ONCOLOGY | 2019年 / 9卷
关键词
mycosis fungoides (MF); Siam Syndrome (SS); cutaneous T-cell lymphomas (CTCL); cancer/testis antigens; germ cell proteins; meiCT; meiomitosis; CANCER-TESTIS ANTIGENS; RETINOIC ACID; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; STRA8; MUTATIONS; LANDSCAPE;
D O I
10.3389/fonc.2019.00429
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer testis (CT) antigens, under normal circumstances are uniquely expressed in testicular germ cells. Recent research has shown that meiosis-specific CT (meiCT) antigens are ectopically expressed in cutaneous T-cell lymphoma (CTCL) and may contribute to increased genomic instability. The aberrant activation of meiosis genes in a mitotic cell is now recognized as a distinctive process, "meiomitosis." We have previously demonstrated the ectopic expression of several meiCT antigens in nine patient-derived CTCL cell lines and in expanded peripheral T lymphocytes isolated from Sezary Syndrome patients. In this study we analyzed the transcriptional expression of meiCT genes in Sezary Syndrome patients and healthy controls using publicly-available RNA sequencing (RNA-Seq) data. We corroborated our in silico analysis by examining the expression of 5 meiCT proteins in formalin-fixed, paraffin-embedded (FFPE) lesional samples from CTCL patients. Our results show significant differential gene expression of STAG3, SGO2, SYCP3, and DMC1 in a cohort of Sezary Syndrome patients when compared to healthy controls. Additionally, our study demonstrates a heterogenous expression of meiCT genes involved in initiation (STRA8), sister chromatin cohesion (STAG3, SGO2), homologous chromosome synapsis (SYCP3) and homologous recombination (DMC1) in atypical lymphocytes in FFPE samples. Our results further confirm the ectopic expression of meiCT genes in CTCL which indicates that CTCL malignant cells likely undergo the process of cancer meiomitosis, as opposed to a typical mitotic division. The ectopic expression of meiCT genes together with investigations into the functional mechanisms of cancer meiomitosis will help provide a foundation to develop novel diagnostic tests to distinguish CTCL from benign inflammatory dermatoses and may enable us to develop additional targeted therapies for patients with this malignancy.
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页数:12
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