Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome.
Marginal zone B-cell lymphomas (MZLs) have been divided into 3 distinct subtypes (extranodal MZLs of mucosa-associated lymphoid tissue [MALT] type, nodal MZLs, and splenic MZLs). Nevertheless, the relationship between the subtypes is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic, and 2 not better specified MZLs) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33 of 218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p, and del(6q23) (TNFAIP3/A20), whereas splenic MZLs was associated with del(7q31), del(8p). Nodal MZLs did not show statistically significant differences compared with MALT lymphoma while lacking the splenic MZLs-related 7q losses. Gains of 3q and 18q were common to all 3 subtypes. del(8p) was often present together with del(17p) (TP53). Although del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZLs.
Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, via Vincenzo Vela 6, Bellinzona, Switzerland.
Andrea
A
Rinaldi
Michael
M
Mian
Ekaterina
E
Chigrinova
Luca
L
Arcaini
Govind
G
Bhagat
Urban
U
Novak
Paola M V
PM
Rancoita
Cassio P
CP
De Campos
Francesco
F
Forconi
Randy D
RD
Gascoyne
Fabio
F
Facchetti
Maurilio
M
Ponzoni
Silvia
S
Govi
Andrés J M
AJ
Ferreri
Manuela
M
Mollejo
Miguel A
MA
Piris
Luca
L
Baldini
Jean
J
Soulier
Catherine
C
Thieblemont
Vincenzo
V
Canzonieri
Valter
V
Gattei
Roberto
R
Marasca
Silvia
S
Franceschetti
Gianluca
G
Gaidano
Alessandra
A
Tucci
Silvia
S
Uccella
Maria Grazia
MG
Tibiletti
Stephan
S
Dirnhofer
Claudio
C
Tripodo
Claudio
C
Doglioni
Riccardo
R
Dalla Favera
Franco
F
Cavalli
Emanuele
E
Zucca
Ivo
I
Kwee
Francesco
F
Bertoni
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D016172:DNA Fingerprinting; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D013160:Splenic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D055815:Young Adult