title: TCRgamma-chain gene rearrangement by GeneScan: incidence and significance of clonal heterogeneity in Sézary syndrome.
abstract: GeneScan (GS) analysis is a highly sensitive method for the early detection of cutaneous T-cell lymphoma (CTCL) and allows the identification of clonal heterogeneity, defined as the coexistence of two or more different T-cell clones in multiple samples from the same patient. We analyzed by GS the incidence and the significance of long-lived oligoclonal expansions in multiple skin and blood samples from 24 Sézary syndrome (SS) patients, and tried to correlate them with the clinical outcome. A skin clonal heterogeneity with additional reproducible TCRgamma-gene rearrangements (TCRgamma-GRs) was detected at diagnosis in 19/24 patients, 13 of whom had a constant prevalence of pathological TCRgamma-GRs in both skin and blood (dominant clonal pattern). During follow-up, an increase in oligoclones that were present at diagnosis or the appearance of new oligoclones was observed in 10 patients; all of them achieved a clinical response to treatment with extracorporeal photochemotherapy (ECP). The TCRgamma pattern (homogeneity or heterogeneity) in the skin at diagnosis showed a relevant prognostic value, and patients with an oligoclonal pattern had a significantly longer survival than those with a homogeneous pattern. In conclusion, multiple-sample approach GS analysis allows the identification of clonal heterogeneity and could also help in identifying SS patients with a potential higher response to therapy.
authors.affiliation: Section of Dermatology, Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy. mariateresa.fierro@unito.it
authors.forename: Maria T
authors.initials: MT
authors.lastname: Fierro
authors.forename: Renata
authors.initials: R
authors.lastname: Ponti
authors.forename: Stefano
authors.initials: S
authors.lastname: Titli
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Comessatti
authors.forename: Mauro
authors.initials: M
authors.lastname: Novelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Fava
authors.forename: Paola Francia
authors.initials: PF
authors.lastname: di Celle
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bernengo
mesh_terms: D005500:Follow-Up Studies; D015321:Gene Rearrangement; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D016133:Polymerase Chain Reaction / Q000379:methods*; D015995:Prevalence; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D012751:Sezary Syndrome / Q000175:diagnosis / Q000235:genetics / Q000401:mortality
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta