Recurrent Chromosomal Aberrations in High Grade B-Cell Lymphomas with IG-MYC Rearrangement and Their Impact on Diagnosis and Survival
R Garcia, AC Seegmiller, A Maleki, R Huang, C Tirado, W Chen. UT Southwestern Medical Center at Dallas, Dallas, TX
Background: Rearrangement (R) of MYC with immunoglobulin genes (IG) is characteristic of Burkitt lymphoma (BL). However, this rearrangement is not entirely specific and is often accompanied by additional cytogenetic abnormalities. The impact of recurrent chromosomal aberrations (RCA) on the classification and survival in IG-MYC rearranged high grade B-cell lymphomas have not yet been well characterized and became the focus of this study.
Design: An institutional database search from 2000-2009 yielded 34 such lymphomas, including 22 BLs, 3 diffuse large B-cell lymphomas (DLBCL), 6 unclassifiable B-cell lymphomas with overlapping features between DLBCL and BL (INT), and 3 plasmablastic lymphomas (PBL), using the 2008 WHO classification scheme. Each diagnostic entity was evaluated for RCA detected by conventional karyotype, and their impact on overall survival was calculated by Kaplan-Meier method and compared by log rank test.
Results: The most frequent RCA in BL were gains of 1q (18.2%), 7p (9%), 12p (13.6%), and loss of 17p (13.6%); in DLBCL losses of 1p32-34, 2p13-25, 4, 9q22-34, 10, 13, 15, R of 5q31-33 and 16p13 (all present in 67% cases); in INT gains of Xp22-q26 (33%), 1q (50%), 8p23-8q24, chromosomes 12 and 20 (33%); and in PBL gain of 1q (67%) and 8p23 R (67%). When comparing RCA between BL and DLBCL, losses of 1p32-34, 2p13-p25, 4p16-q26, 4q32-q36, 9q22-q34, 10, 15p11.2-q24 and 16p13 R were significantly associated with DLBCL (p=0.028). There were significant associations between loss of 15q24-26 and the following aberrations: loss of 10 (p<0.0001), loss of 10q23 (p<0.0001), 12p13 R (p<0.0001) and 3q27 R (p<0.0001), and between non-BL and loss of 10q23 (p=0.01). Univariate analysis showed non-BL, 15q24-26 loss, 12p13-q23 gain, 3q27 R (p<0.01), 1q gain and 10q23 loss (p<0.05) were associated with unfavorable overall survival (p<0.001). Multivariable analysis with stepwise method showed that nBL (p=0.02) and 12p13 R (p=0.02) predicted unfavorable survival.
Conclusions: Each diagnostic entity within MYC rearranged lymphomas carried unique RCA, for example, BL and DLBCL characterized by gains and losses of chromosomes, respectively. This suggests that RCA may play a role in pathogenesis of disease. Moreover, these RCA may not only aid in classifying IG-MYC rearranged B-cell lymphomas, particularly DLBCL versus BL, but also predicting for survival. Specifically, 12p13 R in addition to non-BL was associated with unfavorable clinical outcome.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 179, Wednesday Morning