Molecular aspects of cutaneous T-cell lymphoma : genetic alterations underlying clinical behavior

The research described in the thesis is focused at identifying molecular aberrations contributing to the pathogenesis of CTCL. In search for differences in chromosomal alterations underlying the different clinical behavior and prognosis of patients with mycosis fungoides (MF) and S_zary syndrome (Sz) the DNA copy number alterations of MF were investigated and compared with the previously published profile of Sz. Several alterations of prognostic value were identified. Gene expression data of MF was integrated with DNA copy number alterations to search for genes contributing to tumorigenesis and possible therapeutic targets. With the same purpose gene expression data of MF was compared to normal controls, to identify genes dysregulated otherwise than due to copy number alteration. Additionally miRNA profiles of MF and Sz were elucidated to determine their possible role as gene expression regulator. DNA copy number alterations and gene expression profiles were analyzed of primary cutaneous anaplastic large cell lymphoma and peripheral T cell lymphoma not otherwise specified to gain insight in the molecular mechanisms underlying the different clinical aggressiveness.The studies in this thesis were financially supported by a grant from the Fondation René Touraine (chapter 4 & 5) Financial support for the publication of this thesis was kindly provided by DDL Diagnostic Laboratory, Astellas Pharma B.V., Novartis Pharma B.V., Bauerfeind Benelux B.V., Janssen-Cilag B.V.UBL - phd migration 201

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