Genome-wide analysis of cutaneous T-cell lymphomas identifies three clinically relevant classes.
This study was undertaken to identify recurrent genetic alterations of the three main types of cutaneous T-cell lymphomas (CTCLs): mycosis fungoides (MF), Sézary syndrome (SS), and cutaneous anaplastic large-cell lymphoma (CALCL). Using array-based comparative genomic hybridization, the molecular cytogenetic profiles of 72 samples obtained from 58 patients with CTCL corresponding to 24 transformed MF (T-MF), 16 SS, and 18 CALCLs were determined. T-MF was characterized by gains of 1q25-31, 7p22-11.2, 7q21, 7q31, and 17q12, and losses of 9p21, 10p11.2, and 10q26. SS exhibited gains of 8q23-24.3 and 17q23-24, as well as losses of 9p21, 10p12-11.2, 10q22-24, 10q25-26, and 17p13-q11.1. Finally, CALCL exhibited 6q27 and 13q34 losses. Such imbalances were statistically associated with one CTCL subtype. Unsupervised hierarchical clustering defined three categories of clinical relevance: (1) CALCL apart from epidermotropic-CTCL, (2) an SS-only category, and (3) a mixed category with T-MF and SS cases, with both primary and secondary SS cases. In rare cases, the genetic classification did not correspond to the inclusion diagnosis, possibly reflecting the association of two diseases in the same patient or initial misdiagnosis according to follow-up. Finally, different samples in the same patient clustered together, showing reproducibility of such a classifier.
Laharanne
Elodie
E
Histology and Molecular Pathology EA 2406, University Bordeaux 2, 146 Rue Leo Saignat, Bordeaux, France.
Oumouhou
Naïma
N
Bonnet
Françoise
F
Carlotti
Martina
M
Gentil
Catherine
C
Chevret
Edith
E
Jouary
Thomas
T
Longy
Michel
M
Vergier
Béatrice
B
Beylot-Barry
Marie
M
Merlio
Jean-Philippe
JP
D000465:Algorithms; D004273:DNA, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis / Q000235:genetics; D016410:Lymphoma, T-Cell, Cutaneous / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D009182:Mycosis Fungoides / Q000175:diagnosis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011003:Ploidies; D015203:Reproducibility of Results; D012751:Sezary Syndrome / Q000175:diagnosis / Q000235:genetics; D012878:Skin Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*
D004273:DNA, Neoplasm