Genomic tumor profiling of Sezary Syndrome with high-density oligonucleotide SnP array Free

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Sézary Syndrome (SS) is a peripheral T-cell neoplasm whose etiology and molecular pathogenesis are still unknown. Classical cytogenetics studies have shown that the majority of SS patients have chromosome aberrations; however allelotyping studies and genome-wide surveys for chromosome imbalances in this tumour are still very limited . High-density single nucleotide polymorphism (SNP) arrays enable high-resolution and genome-wide detection of both loss of heterozygosity (LOH) and copy number (CN) abnormality. In this study we used Affymetrix 10K SNP mapping array system to investigate genetic aberrations of an initial group of SS patients consisting of 13 individuals. Tumour and paired normal samples from SS affected individuals were genotyped using GeneChip Human Mapping 10K Array Xba 131 (Affymetrix) containing 11,560 tiled SNPs. Genomic DNA was prepared for hybridisation according to the manufacturer’s instructions. Genotype calls and signal information were obtained using GeneChip Operating Software (GCOS 1.4) and GeneChip DNA Analysis Software (GTYPE4.0). SNP calls were exported to be analysed with DNA-chip Analyser (dChip v1.3+) genotyping software which allows the simultaneous measurement of DNA copy number changes and LOH events.

Our findings identified chromosomes 17p, 10/10q and 9 as the most frequently affected by LOH events, while gains of CN were observed more often for chromosome 17q and 8/8q. Among our patients almost all individuals showing loss of the 17p arm have also gain of the 17q, suggesting the presence of the isochromosome 17q, a frequently reported abnormality in SS. In addition to this, we characterised the chromosome LOH pattern identifying seven regions of significant loss shared by multiple tumours. Sample clustering based on significant LOH regions identified two groups of patients: one of them consists of 4 patients with a lower rate of chromosomal losses while the other contains 9 patients mainly characterised by the co-occurrence of LOH at chromosome 17 and chromosome 10.

The frequency and pattern of chromosomal changes in our group of 13 SS patients are in substantial agreement with previously described results using more conventional techniques, demonstrating the feasibility of the 10K SNP mapping array system to assess allelic imbalance in this tumour. The genome-wide approach and SNP high density allowed the identification of a larger number of LOH regions, including, however, those already described (chromosome 9p, 10q and 17p). Even though no significant statistical association can be observed due to the low number of cases available, we observed a lower overall survival in the group of 9 patients showing simultaneous LOH events at chromosome 17 and 10.