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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1770-1777.
Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2005-02-0542.
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NEOPLASIA
Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma
Hiroyuki Tagawa,
Miyuki Suguro,
Shinobu Tsuzuki,
Keitaro Matsuo,
Sivasundaram Karnan,
Koichi Ohshima,
Masataka Okamoto,
Yasuo Morishima,
Shigeo Nakamura, and
Masao Seto
From the Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; the Japan Biological Informatics Consortium, Tokyo, Japan; the Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan; the First Department of Pathology, Fukuoka University School of Medicine, Fukuoka, Japan; the Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; the Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; and the Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
Diffuse large B-cell lymphoma (DLBCL) comprises molecularly distinct subgroups such as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCLs. We previously reported that CD5+ and CD5-CD10+ DLBCL constitute clinically relevant subgroups. To determine whether these 2 subgroups are related to ABC and GCB DLBCLs, we analyzed the genomic imbalance of 99 cases (36 CD5+, 19 CD5-CD10+, and 44 CD5-CD10-) using array-based comparative genomic hybridization (CGH). Forty-six of these cases (22 CD5+, 7 CD5-CD10+, and 17 CD5-CD10-) were subsequently subjected to gene-expression profiling, resulting in their division into 28 ABC (19 CD5+ and 9 CD5-CD10-) and 18 GCB (3 CD5+, 7 CD5-CD10+, and 8 CD5-CD10-) types. A comparison of genome profiles of distinct subgroups of DLBCL demonstrated that (1) ABC DLBCL is characterized by gain of 3q, 18q, and 19q and loss of 6q and 9p21, and GCB DLBCL is characterized by gain of 1q, 2p, 7q, and 12q; (2) the genomic imbalances characteristic of the CD5+ and CD5-CD10+ groups were similar to those of the ABC and GCB types, respectively. These findings suggest that CD5+ and CD5-CD10+ subgroups are included, respectively, in the ABC and GCB types. Finally, when searching for genomic imbalances that affect patients' prognosis, we found that 9p21 loss (p16INK4a locus) marks the most aggressive type of DLBCL. (Blood. 2005; 106:1770-1777)
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