Oncogenomic analysis of mycosis fungoides reveals major differences with SÈzary syndrome

ABSTRACT: Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is a malignancy of mature, skin-homing T cells. Sézary syndrome (Sz) is often considered to represent a leukemic phase of MF. In this study the pattern of numerical chromosomal alterations in MF tumor samples was defined using array-based CGH; simultaneously gene expression was analyzed using microarrays. Highly recurrent chromosomal alterations in MF include copy number gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. This pattern characteristic of MF differs markedly from chromosomal alterations observed in Sz. Integration of data from array-based CGH and gene expression analysis yielded several candidate genes with potential relevance in the pathogenesis of MF. We confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain, demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes showed diminished expression associated with loss. In addition, it was found that presence of chromosomal alterations on 9p21, 8q24 and 1q21-1q22 was associated with poor prognosis in patients with MF. This study provides novel insight into genetic alterations underlying MF. Furthermore, our analysis uncovered genomic differences between MF and Sz, which suggest that the molecular pathogenesis and therefore therapeutic requirements of these CTCLs may be distinct. To identify candidate oncogenes and tumor suppressor genes residing in chromosomal regions with recurrent copy number alteration in MF. To this end chromosomal alteration and gene expression patterns of 22 MF tumor samples were integrated to determine which genes located in minimal common regions (MCRs) with CNA demonstrated dysregulated expression associated with chromosomal alteration Keywords: aCGH and gene expression integration 22 tumors for aCGH and gene expression

ORGANISM(S): Homo sapiens

SUBMITTER: van Doorn R 

PROVIDER: S-ECPF-GEOD-12902 | biostudies-other | 2009 Jan

REPOSITORIES: biostudies-other