title: Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma.
abstract: 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 (p16(INK4a) locus) marks the most aggressive type of DLBCL.
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tagawa
authors.forename: Miyuki
authors.initials: M
authors.lastname: Suguro
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsuzuki
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Sivasundaram
authors.initials: S
authors.lastname: Karnan
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000145:classification; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification* / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics*; D008875:Middle Aged; D010802:Phylogeny; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor