Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma

Tagawa, Hiroyuki; Suguro, Miyuki; Tsuzuki, Shinobu; Matsuo, Keitaro; Karnan, Sivasundaram; Ohshima, Koichi; Okamoto, Masanori; Morishima, Yasuo; Nakamura, Shigeo; Seto, Masao

doi:10.1182/blood-2005-02-0542

Cited by 194 publications

(191 citation statements)

References 39 publications

(43 reference statements)

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“…Our samples examined also did not include any neuronal tissue, so that the further investigation of the LMO3 expression is valuable for understanding its exact role in both normal and tumor cells. LMO2, also a member of the LMO family, is known as a biomarker of GCB DLBCL 30, 31. Several different characteristics for LMO2 and LMO3 have been described 25; however, our results of association with aggressive clinical features also suggest that LMO3 might have some relevant molecular mechanism in DLBCL cells, as LMO2 does.…”

Section: Discussionmentioning

confidence: 56%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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Diffuse large B‐cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5‐positive (CD5+) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5+ DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5,LMO3,SNAP25,SYT5,SV2C,CABP1,FGF1,FGFR2,NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B‐cell‐like DLBCL (P = 0.046). Compared to the SH3BP5‐negative group, the SH3BP5+ group was correlated with elderly onset (>60 years, P = 0.0096) and advanced‐stage disease (stage III/IV, P = 0.037). The LMO3+ group showed a worse performance status (>1, P = 0.0004). The SH3BP5+ group and the LMO3+ group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab‐containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.

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Section: Discussionmentioning

confidence: 56%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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“…To date, array-CGH studies on NHL have focused mainly on target gene identification rather than clinical correlations. 13,28 Furthermore, those series have not included patients who were treated prospectively and homogeneously.…”

Section: Discussionmentioning

confidence: 99%

Array comparative genomic hybridization identifies genetic regions associated with outcome in aggressive diffuse large B‐cell lymphomas

Robledo¹,

Garcı́a²,

Caballero³

et al. 2009

Cancer

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BACKGROUND: Diffuse large B‐cell lymphomas (DLBCLs) are the most common type of non‐Hodgkin lymphomas. With chemotherapy and progenitor stem cell transplantation, about 60% of patients with DLBCL are long‐term survivors. The International Prognostic Index identifies patients with different outcomes. However, biologic characteristics also may help to discriminate different treatments groups. METHODS: DNA copy number changes identified by array comparative genomic hybridization (array‐CGH) were studied in 40 patients who had DLBCL with a poor prognosis and who were treated uniformly with dose‐escalated cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and intensification before high‐dose chemotherapy with autologous stem cell transplantation. RESULTS: In total, 722 copy number changes were observed (median, 5 copy number changes per patient; range, 0‐75 copy number changes per patient), with a predominance of gains. Gains on 2p16 were present only in patients who failed to achieve a complete response after escalated CHOP therapy (P < .05). In univariate analysis, gains on 2p16 and losses on 17p13 (the tumor protein p53 gene TP53 gene) were associated with a poor response to the therapy. Furthermore, age >60 years and losses on 10q23.31 (the phosphatase and tensin homolog gene PTEN) or on 17p13 were associated with short survival. In multivariate analysis, only advanced age and losses on 10q23.31 retained an adverse prognostic impact. CONCLUSIONS: Array‐CGH identified multiple regions with common copy number changes, some of which were associated with outcome in patients with DLBCL. Cancer 2009. © 2009 American Cancer Society.

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“…1,2 Extensive analyses of gene expression profiles [3][4][5] and genomic copy number [6][7][8][9] in DLBCL have provided valuable insights into their cellular origins and the molecular bases for their variable clinical behaviors. For example, gene expression analyses have identified two major DLBCL subtypes, germinal center B-celllike (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL), that originate from different stages of normal B-cell development.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

et al. 2008

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In an initial epigenetic characterization of diffuse large B-cell lymphoma (DLBCL), we evaluated the DNA methylation levels of over 500 CpG islands. Twelve CpG islands (AR, CDKN1C, DLC1, DRD2, GATA4, GDNF, GRIN2B, MTHFR, MYOD1, NEU-ROD1, ONECUT2 and TFAP2A) showed significant methylation in over 85% of tumors. Interestingly, the methylation levels of a CpG island proximal to FLJ21062 differed between the activated B-cell-like (ABC-DLBCL) and germinal center B-cell-like (GCB-DLBCL) subtypes. In addition, we compared the methylation and expression status of 67 genes proximal (within 500 bp) to the methylation assays. We frequently observed that hypermethylated CpG islands are proximal to genes that are expressed at low or undetectable levels in tumors. However, many of these same genes were also poorly expressed in DLBCL tumors where their cognate CpG islands were hypomethylated. Nevertheless, the proportional reductions in BNIP3, MGMT, RBP1, GATA4, IGSF4, CRABP1 and FLJ21062 expression with increasing methylation suggest that epigenetic processes strongly influence these genes. Lastly, the moderate expression of several genes proximal to hypermethylated CpG tracts suggests that DNA methylation assays are not always accurate predictors of gene silencing. Overall, further investigation of the highlighted CpG islands as potential clinical biomarkers is warranted.

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Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma

Cited by 194 publications

References 39 publications

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Array comparative genomic hybridization identifies genetic regions associated with outcome in aggressive diffuse large B‐cell lymphomas

DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

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