Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities.
Lymphoplasmacytic lymphomas and marginal zone lymphomas of nodal, extra-nodal and splenic types account for 10% of non-Hodgkin lymphomas. They are similar at the cell differentiation level, sometimes making difficult to distinguish them from other indolent non-Hodgkin lymphomas. To better characterize their genetic basis, we performed array-based comparative genomic hybridization in 101 marginal zone lymphomas (46 MALT, 35 splenic and 20 nodal marginal zone lymphomas) and 13 lymphoplasmacytic lymphomas. Overall, 90% exhibited copy-number abnormalities. Lymphoplasmacytic lymphomas demonstrated the most complex karyotype (median=7 copy-number abnormalities), followed by MALT (4), nodal (3.5) and splenic marginal zone lymphomas (3). A comparative analysis exposed a group of copy-number abnormalities shared by several or all the entities with few disease-specific abnormalities. Gain of chromosomes 3, 12 and 18 and loss of 6q23-q24 (TNFAIP3) were identified in all entities. Losses of 13q14.3 (MIRN15A-MIRN16-1) and 17p13.3-p12 (TP53) were found in lymphoplasmacytic and splenic marginal zone lymphomas; loss of 11q21-q22 (ATM) was found in nodal, splenic marginal zone and lymphoplasmacytic lymphomas and loss of 7q32.1-q33 was found in MALT, splenic and lymphoplasmacytic lymphomas. Abnormalities affecting the nuclear factor kappa B pathway were observed in 70% of MALT and lymphoplasmacytic lymphomas and 30% of splenic and nodal marginal zone lymphomas, suggesting distinct roles of this pathway in the pathogenesis/progression of these subtypes. Elucidation of the genetic alterations contributing to the pathogenesis of these lymphomas may guide to design-specific therapeutic approaches.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, AZ, USA.
Esteban
E
Braggio
Ahmet
A
Dogan
Jonathan J
JJ
Keats
Wee J
WJ
Chng
Gaofeng
G
Huang
Julie M
JM
Matthews
Matthew J
MJ
Maurer
Mark E
ME
Law
David S
DS
Bosler
Michael
M
Barrett
Izidore S
IS
Lossos
Thomas E
TE
Witzig
Rafael
R
Fonseca
D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000473:pathology*; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000473:pathology*
D004273:DNA, Neoplasm