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.
Espinet
Blanca
B
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
Salaverria
Itziar
I
Beà
Sílvia
S
Ruiz-Xivillé
Neus
N
Balagué
Olga
O
Salido
Marta
M
Costa
Dolors
D
Carreras
Joaquim
J
Rodríguez-Vicente
Ana Eugenia
AE
Luís García
Juan
J
Hernández-Rivas
Jesús María
JM
Calasanz
María José
MJ
Siebert
Reiner
R
Ferrer
Ana
A
Salar
Antonio
A
Carrió
Ana
A
Polo
Natividad
N
García-Marco
José Antonio
JA
Domingo
Alicia
A
González-Barca
Eva
E
Romagosa
Vicenç
V
Marugán
Isabel
I
López-Guillermo
Armando
A
Millá
Fuensanta
F
Luís Mate
José
J
Luño
Elisa
E
Sanzo
Carmen
C
Collado
Rosa
R
Oliver
Isabel
I
Monzó
Sebastià
S
Palacín
Antonio
A
González
Teresa
T
Sant
Francesc
F
Salinas
Ramon
R
Ardanaz
María Teresa
MT
Font
Llorenç
L
Escoda
Lourdes
L
Florensa
Lourdes
L
Serrano
Sergi
S
Campo
Elias
E
Solé
Francesc
F
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