The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL)
- 14 June 2015
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 21 (12), 2820-2829
- https://doi.org/10.1158/1078-0432.ccr-14-3322
Abstract
Purpose: Although many patients with mycosis fungoides presenting with stage I disease enjoy an indolent disease course and normal life expectancy, about 15% to 20% of them progress to higher stages and most ultimately succumb to their disease. Currently, it is not possible to predict which patients will progress and which patients will have a stable disease. Previously, we conducted microarray analyses with RT-PCR validation of gene expression in biopsy specimens from 60 patients with stage I–IV cutaneous T-cell lymphoma (CTCL), identified three distinct clusters based upon transcription profile, and correlated our molecular findings with 6 years of clinical follow-up. Experimental Design: We test by RT-PCR within our prediction model the expression of about 240 genes that were previously reported to play an important role in CTCL carcinogenesis. We further extend the clinical follow-up of our patients to 11 years. We compare the expression of selected genes between mycosis fungoides/Sézary syndrome and benign inflammatory dermatoses that often mimic this cancer. Results: Our findings demonstrate that 52 of the about 240 genes can be classified into cluster 1–3 expression patterns and such expression is consistent with their suggested biologic roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and TOX) are able to both identify patients who are at risk of progression and also distinguish mycosis fungoides/Sézary syndrome from benign mimickers. Conclusions: This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and treatment of CTCL. Clin Cancer Res; 21(12); 2820–9. ©2015 AACR.Keywords
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This publication has 56 references indexed in Scilit:
- The role of AHI1 and CDKN1C in cutaneous T‐cell lymphoma progressionExperimental Dermatology, 2012
- Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell LymphomaPLOS ONE, 2012
- Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1βNature, 2012
- Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviorsBlood, 2010
- Transcriptional Profiles Predict Disease Outcome in Patients with Cutaneous T-Cell LymphomaClinical Cancer Research, 2010
- Poor prognosis in non-Caucasian patients with early-onset mycosis fungoidesJournal of the American Academy of Dermatology, 2009
- Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcomeBlood, 2007
- Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)Blood, 2007
- Microarray validation: factors influencing correlation between oligonucleotide microarrays and real-time PCRBiological Procedures Online, 2006
- Familial mycosis fungoides: Report of 6 kindreds and a study of the HLA systemJournal of the American Academy of Dermatology, 2005