T cell receptor-gamma gene analysis of CD30+ large atypical individual cells in CD30+ large primary cutaneous T cell lymphomas.
The hallmark of primary cutaneous CD30+ large T cell lymphoma are large lymphoid tumor cells, at least 75% of which, by definition, must be positive for CD30. The relatively benign clinical course of this lymphoma type has been explained with CD30-induced apoptosis, on the assumption that expression of CD30 defines the tumor clone; however, this hypothesis has not been tested on the molecular level to date. In this study we analyzed CD30+ cells in four patients with primary cutaneous CD30+ large T cell lymphoma by single cell polymerase chain reaction of T cell receptor-gamma genes followed by sequencing. Here, we demonstrate that most of the large CD30+ atypical cells possessed identical T cell receptor-gamma gene rearrangements, indicative of clonal proliferation. Nevertheless, polyclonally rearranged T cells were present in all CD30+ samples studied. In addition, one patient showed a second clone in a separate biopsy and three of four patients showed chromosomal imbalances as revealed by comparative genomic hybridization. Taken together, our data suggest that the CD30+ population in primary cutaneous CD30+ large T cell lymphoma indeed contains the tumor clone, thus providing molecular support for a link between clinical course and CD30-related signaling. Importantly, however, CD30 expression does not define the tumor clone as bystander T cells, as well as occasional additional clones, are also present in this population.
Gellrich
Sylke
S
Department of Dermatology, Medical Faculty (Charité), Humboldt-University, Berlin, Germany. Sylke.Gellrich@charite.de
Wilks
Anke
A
Lukowsky
Ansgar
A
Wernicke
Martin
M
Müller
Astrid
A
Marcus Muche
J
J
Fischer
Tanja
T
Jasch
Kim Christian
KC
Audring
Heike
H
Sterry
Wolfram
W
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002999:Clone Cells; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis; D016410:Lymphoma, T-Cell, Cutaneous / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
D017730:Ki-1 Antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta