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.

Biased use of the IGHV4 family and evidence for antigen selection in Chlamydophila psittaci-negative ocular adnexal extranodal marginal zone lymphomas.

Extranodal marginal zone lymphomas (EMZL) are the most common lymphomas in the ocular adnexa. The etiology and potential role for antigenic stimulation in these lymphomas are still controversial. We have examined IGHV gene usage and mutations in 67 Chlamydophila psittaci-negative ocular adnexal EMZL. Clonal IGHV gene sequences were identified in 43 tumors originating from the orbit (19), conjunctivae (18) and lacrimal gland (6). Forty four potentially functional clonal IGHV gene sequences were detected with overrepresentation of the IGHV4 family and IGHV4-34 gene. All but 3 sequences were mutated with the average percent homology to the germ line of 93.5±6.1. Multinomial model and Focused binomial test demonstrated evidence for positive and/or negative antigen selection in 59% of the potentially functional IGHV genes. Intraclonal variation was detected in 8 of 11 tumor specimens. Overall our findings demonstrate that C. psittaci-negative ocular adnexal EMZL exhibit biased usage of IGHV families and genes with evidence for intraclonal heterogeneity and antigen selection in multiple tumors, implicating B-cell receptor-mediated antigen stimulation in the pathogenesis of these lymphomas.

Ocular Adnexal Lymphoma: no evidence for bacterial DNA associated with lymphoma pathogenesis.

Ocular Adnexal Lymphomas (OALs) are the most common tumors of the eye, the majority being extranodal mucosa-associated lymphoid tissue (MALT) lymphomas. Association with Chlamydia psittaci was described in some geographic areas. OAL response to antibiotic therapy was reported in cases not harboring Chlamydia psittaci DNA, suggesting that other bacterial infection might be implicated in the pathogenesis. We examined 49 MALT OALs for bacterial DNA using two distinct polymerase chain reaction techniques based on universal bacterial primers. No bacterial DNA that could be implicated in OAL pathogenesis was detected, suggesting that bacterial infection is not associated with OAL in South Florida.