Array-comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B-cell lymphoma shows distinct genomic alterations
Version of Record online: 24 MAR 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 105, Issue 4, pages 481–489, April 2014
How to Cite
Cancer Sci 105 (2014) 481–489
- Issue online: 11 APR 2014
- Version of Record online: 24 MAR 2014
- Accepted manuscript online: 14 FEB 2014 04:04PM EST
- Manuscript Accepted: 31 JAN 2014
- Manuscript Revised: 16 JAN 2014
- Manuscript Received: 24 SEP 2013
- Ministry of Health, Labor and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science
- Foundation of Promotion of Cancer Research
- Japan Leukemia Research Fund
- National Natural Science Foundation of China. Grant Number: 81071951
- Array-comparative genomic hybridization;
- diffuse large B-cell lymphoma;
- genomic profiling;
- lymphoma classification
Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic and molecular levels. Subtypes include germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL, according to microarray analysis, and germinal center type or non-germinal center type by immunohistochemistry. Although some reports have described genomic aberrations based upon microarray classification system, genomic aberrations based upon immunohistochemical classifications have rarely been reported. The present study aimed to ascertain the relationship between genomic aberrations and subtypes identified by immunohistochemistry, and to study the pathogenetic character of Chinese DLBCL. We conducted immunohistochemistry using antibodies against CD10, BCL6 and MUM1 in 59 samples of DLBCL from Chinese patients, and then performed microarray-based comparative genomic hybridization for each case. Characteristic genomic differences were found between GCB and non-GCB DLBCL from the array data. The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non-GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05). We found completely different mutations in BCL6+ and BCL6− non-GCB type DLBCL, whereby the BCL6− group had a higher number of gains at 1q and a loss at 14q32.13 (P ≤ 0.005), while the BCL6+ group showed a higher number of gains at 14q23.1 (P = 0.15) and losses at 6q (P = 0.07). The BCL6− group had a higher frequency of genomic imbalances compared to the BCL6+ group. In conclusion, the BCL6+ and BCL6− non-GCB type of DLBCL appear to have different mechanisms of pathogenesis.