Functional copy number changes in Sézary syndrome: toward an integrated molecular cytogenetic map III.
Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphomas (CTCL) manifested by generalized exfoliative erythroderma, intense pruritus, peripheral lymphadenopathy, and abnormal hyperchromatic mononuclear cells in the skin, lymph nodes, and peripheral blood. Previous studies have revealed complex genetic aberrations affecting almost all chromosomes with up- and down-regulation of several genes in this subtype of CTCL. It is still unclear, however, which of these genetic alterations are the primary changes and which are the secondary ones. We have long thought that a key molecular defect should be consistently present at DNA, RNA, and protein levels. We therefore assume that some chromosome copy number changes (CNC) seen in cancer cells may have a direct impact on gene expression pattern and that these CNC are presumably functional. To test this hypothesis, we designed a simple but novel boinformatic method that included analysis of SS gene expression microarray raw data, generation of gene lists from the chromosomal regions showing significant CNC in SS, and data remaining to establish if the CNC gene lists affected gene clustering in terms of separation of SS cases from the normal controls or not. The bioinformatic analysis of 17 selected gene lists with GeneSpring software showed that four (24%) from copy number losses at 1p36p22, 6q24, and 15q11.2, as well as gains at 22q11.2q13.3, were capable of separating all six SS cases from two controls (P<0.05), and some of the genes, such as LCK at 1p34.3, may have implications in CTCL. The remaining 13 gene lists produced a mixed gene clustering patterns between SS cases and normal control samples (P<<0.01). These findings suggest that CNC from these chromosomal regions may be functional and relevant to SS.
Mao
Xin
X
Centre for Cutaneous Research, Institute of Cell and Molecular Sciences, Bartz and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. mxmayo@yahoo.co.uk
McElwaine
Suzanne
S
D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D006801:Humans; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D012751:Sezary Syndrome / Q000235:genetics*