Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.
Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.
Salgado
Rocío
R
Laboratori de Citogènetica Molecular, Servei de Patologia, IMIM-Hospital del Mar, Barcelona, Spain.
Servitje
Octavio
O
Gallardo
Fernando
F
Vermeer
Maarten H
MH
Ortiz-Romero
Pablo L
PL
Karpova
Maria B
MB
Zipser
Marie C
MC
Muniesa
Cristina
C
García-Muret
María P
MP
Estrach
Teresa
T
Salido
Marta
M
Sánchez-Schmidt
Júlia
J
Herrera
Marta
M
Romagosa
Vicenç
V
Suela
Javier
J
Ferreira
Bibiana I
BI
Cigudosa
Juan C
JC
Barranco
Carlos
C
Serrano
Sergio
S
Dummer
Reinhard
R
Tensen
Cornelis P
CP
Solé
Francesc
F
Pujol
Ramon M
RM
Espinet
Blanca
B
D001706:Biopsy; D055028:Comparative Genomic Hybridization; D005819:Genetic Markers; D005820:Genetic Testing; D042822:Genomic Instability; D006801:Humans; D009182:Mycosis Fungoides / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012867:Skin / Q000473:pathology; D016019:Survival Analysis
D005819:Genetic Markers