Incidence and prognostic impact of secondary cytogenetic aberrations in a series of 145 patients with mantle cell lymphoma.
Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with an aggressive behavior, characterized by the t(11;14)(q13;q32). Several secondary genetic abnormalities with a potential role in the oncogenic process have been described. Studies of large MCL series using conventional cytogenetics, and correlating with proliferation and survival, are scarce. We selected 145 MCL cases at diagnosis, displaying an aberrant karyotype, from centers belonging to the Spanish Cooperative Group for Hematological Cytogenetics. Histological subtype, proliferative index and survival data were ascertained. Combined cytogenetic and molecular analyses detected CCND1 translocations in all cases, mostly t(11;14)(q13;q32). Secondary aberrations were present in 58% of patients, the most frequent being deletions of 1p, 13q and 17p, 10p alterations and 3q gains. The most recurrent breakpoints were identified at 1p31-32, 1p21-22, 17p13, and 1p36. Aggressive blastoid/pleomorphic variants displayed a higher karyotypic complexity, a higher frequency of 1p and 17p deletions and 10p alterations, a higher proliferation index and poor survival. Gains of 3q and 13q and 17p13 losses were associated with reduced survival times. Interestingly, gains of 3q and 17p losses added prognostic significance to the morphology in a multivariate analysis. Our findings confirm previous observations indicating that proliferation index, morphology and several secondary genetic alterations (3q gains and 13q and 17p losses) have prognostic value in patients with MCL. Additionally, we observed that 3q gains and 17p losses detected by conventional cytogenetics are proliferation-independent prognostic markers indicating poor outcome.
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Servei d'Hematologia Clínica, GRETNHE, IMIM-Hospital del Mar, Barcelona, Spain. bespinet@imas.imim.es
Blanca
B
Espinet
Itziar
I
Salaverria
Sílvia
S
Beà
Neus
N
Ruiz-Xivillé
Olga
O
Balagué
Marta
M
Salido
Dolors
D
Costa
Joaquim
J
Carreras
Ana Eugenia
AE
Rodríguez-Vicente
Juan
J
Luís García
Jesús María
JM
Hernández-Rivas
María José
MJ
Calasanz
Reiner
R
Siebert
Ana
A
Ferrer
Antonio
A
Salar
Ana
A
Carrió
Natividad
N
Polo
José Antonio
JA
García-Marco
Alicia
A
Domingo
Eva
E
González-Barca
Vicenç
V
Romagosa
Isabel
I
Marugán
Armando
A
López-Guillermo
Fuensanta
F
Millá
José
J
Luís Mate
Elisa
E
Luño
Carmen
C
Sanzo
Rosa
R
Collado
Isabel
I
Oliver
Sebastià
S
Monzó
Antonio
A
Palacín
Teresa
T
González
Francesc
F
Sant
Ramon
R
Salinas
María Teresa
MT
Ardanaz
Llorenç
L
Font
Lourdes
L
Escoda
Lourdes
L
Florensa
Sergi
S
Serrano
Elias
E
Campo
Francesc
F
Solé
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048708:Cell Growth Processes / Q000235:genetics; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D015331:Cohort Studies; D019938:Cyclin D1 / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models
C530104:CCND1 protein, human; D019938:Cyclin D1