Gistic Evaluation in Sezary Syndrome
Authors: Cristofoletti Cristina , Tocco Valeria , Narducci Maria Grazia , Scala Enrico , Berti Emilio , Frontani Marina , Lombardo Giuseppe Alfonso , Monopoli Alessandro , Citterich Mauro Helmer , Bresin Antonella , Picchio Maria Cristina , Russo Giandomenico , Caprini Elisabetta 
Published: October 2019

Abstract
Abstract 4814
Sezary Syndrome (SS) is characterized by specific chromosomal abnormalities, however is not completely clarified yet which are the genetics hits associated to the initial phase or associated to disease progression. In this study, employing both high density Comparative Genomic Hybridization array (aCGH) and Single Nucleotide Polymorphism (SNP) array technologies, we elucidated the most frequent and significant chromosomal gain and loss regions, and new potentially relevant aberration for the disease progression onset.
A total of 30 samples derived from 18 SS patients were analyzed on the Gene Chip Human Mapping 10K Array (Affymetrix). Genotype call and signal information performed by dChip SNP Software (http://www.dchip.org) provided us normalization and simultaneous measurement of Loss of Heterozygosity (LOH) and DNA Copy Number (CN) changes. We have further refined our analysis with a systematic method, Genomic Identification of Significant Targets in Cancer (GISTIC), able to identify regions that were significantly amplified o deleted, assigning a G-score that considers the amplitude of the aberration as well as the frequency of its occurrence across samples (http://genepattern.broadinstitute.org). Our data, generating by the integration of this two methods (see Table 1), revealed 19 significant focal event, including 10 amplification (10p, 17q, 8q, 6p, 4p, 1q, 18q, 21q, 3q, 1p) and 9 deletions (14q, 17p, 10p, 9p, 8p, 13q, 12p, 6q, 2p).
In addition, new significant aberrant regions were identified, such as losses of 9p21.3, locus of an important tumor-suppressor gene CDKN2A (p16INK4a/p14ARF) and CDKN2B (p15INK4b). Recently, several study have reported the great influence of alteration in p16INK4a/p14ARF for prognosis of Diffuse large B-cell lymphoma (DLBL), primary cutaneous DLBCL leg-type, Blastic plasmacytoid dendritic cell neoplasm (BPDCN). Across our set of samples, 9p21.3 deletion occur in 8/30 samples from 6 patient, prevalently in heterozygosity state (Log2 ratio from −0.3484 to –0.7691). Two cases presented homozygous deletion (Log2 ratio from −1.2157 to –1.5342), and in four patients losses appeared only in a following phase of observation, suggesting a tumor progression event.
Table 1 Significant regions of chromosomal gain Genes in Region Significant regions of chromosomal loss Genes in Region Cytoband Q value GISTIC peak Cytoband Q value GISTIC peak 10p12.33 8.07E-13 17765313-19264851 8 14q11.2 1.85E-40 21395737-22130391 1 17q11.1 3.54E-09 20147238-62034035 563 17p13.1 2.15E-10 1-15053486 234 8q22.3 2.93E-07 70887466-146274826 314 10p11.22 1.98E-07 30280444-32664641 8 6p25.3 0.0020062 1-1263549 6 9p21.3 0.00074825 21283632-22089567 11 4p15.32 0.0071803 17395812-20340589 4 8p23.3 0.00076308 1-32177352 179 1q23.3 0.039674 158849705-159641626 8 13q21.31 0.0028295 63681448-65120691 0 18q22.3 0.1913 1-76117153 251 12p13.1 0.025412 9304151-17414118 85 21q22.3 0.1913 1-46944323 223 6q24.1 0.029124 139319577-141635965 4 3q29 0.2191 169050880-199505740 163 2p23.3 0.043403 24636437-43910832 126 1p36.31 0.11633 1-20338260 239

Disclosures:
No relevant conflicts of interest to declare.