Cutaneous anaplastic large cell lymphoma and peripheral T-cell lymphoma NOS show distinct chromosomal alterations and differential expression of chemokine receptors and apoptosis regulators.
Primary cutaneous anaplastic large cell lymphoma (C-ALCL) has an indolent clinical course and favorable prognosis. On the contrary, primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTL-NOS) shows aggressive clinical behavior. To identify genomic events relevant in the pathogenesis of these cutaneous T-cell lymphomas (CTCLs), we carried out array-based comparative genomic hybridization (CGH) analysis. Simultaneously, gene expression profiling was conducted to gain insight into gene expression programs associated with the different clinical behavior of these CTCLs. C-ALCL was characterized by gains on chromosome 7q and 17q and losses on 6q and 13q. PTL-NOS similarly showed gains on 7q and 17q, but was distinguished by gains on chromosome 8 and loss of a focal overlapping region on 9p21. We identified minimal common regions harboring candidate oncogenes and tumor suppressor genes in C-ALCL and PTL-NOS. Genes with a role in lymphocyte chemotaxis, apoptosis, and proliferation were overrepresented among genes differentially expressed between these lymphomas. C-ALCL showed higher expression of the skin-homing chemokine receptor genes CCR10 and CCR8, which may explain the lower tendency to disseminate to extracutaneous sites. Furthermore, C-ALCL and PTL-NOS showed aberrant expression of distinct genes implicated in apoptosis and proliferation, such as IRF4/MUM1 and PRKCQ, which may account for differences in clinical aggressiveness.
van Kester
Marloes S
MS
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Tensen
Cornelis P
CP
Vermeer
Maarten H
MH
Dijkman
Remco
R
Mulder
Aat A
AA
Szuhai
Karoly
K
Willemze
Rein
R
van Doorn
Remco
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018925:Chemokines / Q000378:metabolism; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000378:metabolism*; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism*
D018925:Chemokines