Identification of key regions and genes important in the pathogenesis of sezary syndrome by combining genomic and expression microarrays.
In this study, we used single nucleotide polymorphism and comparative genomic hybridization array to study DNA copy number changes and loss of heterozygosity for 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 >30% of tumors: 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. Integrating mapping and transcriptional data, 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-kappaB pathway (BAG4, BTRC, NKIRAS2, PSMD3, and 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, such as BUB3 and PIP5K1B. Altogether, our study confirms and maps more precisely the regions of gain and loss and, combined to transcriptional profiles, suggests a novel set of genes of potential interest in SS.
Caprini
Elisabetta
E
Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico and National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
Cristofoletti
Cristina
C
Arcelli
Diego
D
Fadda
Paolo
P
Citterich
Mauro Helmer
MH
Sampogna
Francesca
F
Magrelli
Armando
A
Censi
Federica
F
Torreri
Paola
P
Frontani
Marina
M
Scala
Enrico
E
Picchio
Maria Cristina
MC
Temperani
Paola
P
Monopoli
Alessandro
A
Lombardo
Giuseppe Alfonso
GA
Taruscio
Domenica
D
Narducci
Maria Grazia
MG
Russo
Giandomenico
G
D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate
D009363:Neoplasm Proteins; D012333:RNA, Messenger