Molecular cytogenetic characterization of Sézary syndrome

Sézary syndrome (SS) is a rare form of erythrodermic cutaneous T-cell lymphoma with hematological involvement and a poor prognosis. At present little is known about the molecular pathogenesis of this malignancy. To address this issue, we analyzed 28 SS cases through the use of molecular cytogenetic techniques. Conventional cytogenetic analysis showed 12 of 28 cases with clonal chromosome abnormalities (43%). Seven cases had aberrations affecting chromosomes 1 and 17; five demonstrated rearrangement of chromosomes 10 and 14; four presented with an abnormality of 6q. Multiplex-fluorescence in situ hybridization (M-FISH) revealed complex karyotypes in 6 of 17 cases (35%), and recurrent der(1)t(1;10)(p2;q2) and der(14)t(14;15)(q;q?) translocations were each identified in two cases, and confirmed by dual-color FISH. There was an overall difference in the incidence of clonal abnormalities detected by G-banded karyotyping and M-FISH. In addition, comparative genomic hybridization studies revealed chromosome imbalances (CIs) in 9 of 20 cases (45%), with a mean DNA copy number change per sample of 1.95 +/- 2.74, and losses (mean: 1.25 +/- 1.77) more frequent than gains (mean: 0.7 +/- 1.26). The most common CIs noted were loss of 1p, followed by losses of 10/10q, 17p, and 19, and gains of 17q and 18. Furthermore, in conjunction with this study a systematic literature review was conducted, which showed a high frequency and consistent pattern of chromosome changes in SS. These findings suggest that chromosomal instability is common in SS, although there are specific chromosomal abnormalities that appear to be characteristic, and the identification of two different recurrent chromosome translocations provides the basis for further studies.