Combined High Resolution Genomic and Expression Profiles Microarray Analysis in Sezary Syndrome.

Abstract 3238

Poster Board III-175

We have used single nucleotide polymorphism (SNP) and comparative genomic hybridization array (aCGH) to study DNA copy number (CN) changes and loss of heterozygosity (LOH) in a series of 28 patients affected by Sézary syndrome (SS), a rare form of cutaneous-T-cell lymphoma (CTCL). Our data identified, further confirming previous studies, recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71 and 68% of cases respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in more than 30% of tumours: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. Individual chromosomal aberrations did not show a significant correlation with prognosis, however when more than three recurrent chromosomal alterations (gain or loss) were considered, a statistical association was observed using Kaplan-Meier survival analysis. Crossing genomic data mapping with those obtained from gene expression profiles of matching samples we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer related genes such as members of the NF-kB pathway (NKIRAS2, PSMD3, BAG4, BTRC, TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times we identify several common candidates that might exert critical roles in SS, like PIP5K1B and BUB3. Taken together this study confirms and maps more precisely the regions of gain and loss and, combined to transcriptional profiles, suggest a novel set of genes of potential interest in SS.