Comparative Genomic Hybridization Array of Angioimmunoblastic T-Cell Lymphomas with and without Large B-Cell Proliferations
JH Kurzer, L Ma, DA Arber. Stanford University Medical Center, Stanford, CA
Background: Angioimmunoblastic T-cell lymphoma (AILT) is an aggressive peripheral T-cell lymphoma (PTCL) occurring in middle-aged and elderly adults. A common finding among AILT and other PTCL is an EBV-associated large B-cell proliferation. Genomic differences between AILT and AILT with large B-cell proliferations (AILT LB) previously have not been studied. The current study aims to characterize gene dosage changes separating AILT from AILT LB and other lymphomas.
Design: 5 AILT cases, 5 AILT LB, 5 PTCL, and 5 diffuse large B-cell lymphomas (DLBCL), diagnosed at Stanford University were studied. DNA was isolated from paraffin blocks and all 20 cases were hybridized to the Agilent Human Genome CGH 4 x 44 K Microarray using Agilent's Protocol (Agilent Technologies, Santa Clara, CA). Agilent Genomic Workbench Standard Edition 5.0.00 was used to analyze the data, using the ADM-2 aberration algorithm, with a 3.5 threshold.
Results: Genomic alterations in AILT seen in previous studies were again demonstrated in the current study, such as gains in 22q, 19, 11(p11-q14), and losses in 13q. Gene amplifications exclusive to AILT include SHCBP1 (16q11.2, 80%), while AILT-exclusive deletions include ST8SIA4 (5q21.1, 60%), SH2B3 and ATXN2 (12q24.12, 60%). In contrast, PHF (20q11.22) was found exclusively amplified in AILT LB (60%). Interestingly, AILT and DLBCL, but not AILT LB were found to have FLT1 (13q12.3) deletions. T- lymphoma-specific gene gains include WDR21A (14q24.2, 60% AILT, 80% AILT LB, 60% PTCL), while deletions include CKS2 (9q22.2, 80% AILT, 40% AILT LB, 40% PTCL). Gene amplifications found amongst all studied lymphoma-types include ANKRD44 (2q33.1, 40% AILT, 80% AILT LB, 80% DLBCL, 40% PTCL) and CFLAR (2q33.1, 20% AILT, 60% AILT LB, 60% DLBCL, 60% PTCL), while common deletions include ANGEL2 (1q32.3, 40% AILT, 20% AILT LB, 60% DLBCL, 40% PTCL), ECT2 (3q26.31, 80% AILT, 60% AILT LB, 40% DLBCL, 40% PTCL), and PRDM2 (1q36.21, 60% AILT, 20% AILT LB, 20% DLBCL, 20% PTCL).
Conclusions: The finding of gene amplifications (SHCBP1) and deletions (ST8SIA4, SH2B3, and ATXN2) that separate AILT from other lymphomas, as well as AILT from AILT LB, raises the possibility that the lack of these alterations provides a favorable environment for B-cell proliferations to arise. In addition the T-cell lymphoma-specific gene alterations, WDR21A and CKS2, as well as the more universal alterations (ANKRD44, ECT2, CFLAR, ANGEL2, and PRDM2) provide possible clues for genetic driving forces within T-cell lymphomas and lymphomas in general.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 195, Tuesday Morning