Gene expression and angiotropism in primary CNS lymphoma

Rubenstein, James L.; Fridlyand, Jane; Shen, Arthur; Aldape, Kenneth; Ginzinger, David G.; Batchelor, Tracy T.; Treseler, Patrick A.; Berger, Mitchel; McDermott, Michael; Prados, Michael D.; Karch, Jon; Okada, Craig; Hyun, William C.; Parikh, Seema; Haqq, Chris; Shuman, Marc A.

doi:10.1182/blood-2005-03-0897

Cited by 192 publications

(190 citation statements)

References 41 publications

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“…Although of high clinical interest, a correlation of these subgroups with prognosis is hampered by the still limited number of PCNSL available for gene expression profiling and awaits further studies. These data are in accordance with recent observations in a series of 23 PCNSL, 14 which were equally represented in the two histogenetic and the unclassifiable subgroups of DLBCL as defined by gene expression profiling. 16 Thus, our results further support the notion that PCNSL exhibit characteristics associated with both ABC (IGM expression with absence of IG class switch, high frequency of somatic mutations of IG genes, recurrent 18q21 gains, activation of the nuclear factor-kB (NF-kB) pathway, high expression of BCL2 mRNA and protein 1,[17][18][19] ) and GCB type (expression of BCL6, ongoing somatic hypermutation 1,20 ) DLBCL.…”

Section: Discussionsupporting

confidence: 80%

“…A CNS-specific impact may also account at least in part for differences in the gene expression pattern between PCNSL and systemic DLBCL as reported by Rubenstein et al 14 These authors observed more than 460 ESTs to be significantly differently expressed between 23 PCNSL and 9 DLBCL and published a list of 29 ESTs to be most differentially expressed between these two lymphoma entities. In these analyses, genes highly expressed in CNS tissue have been excluded in a different way.…”

Section: Discussionmentioning

confidence: 77%

“…In fact, the unsupervised analysis of gene expression profiles Figure 2 Expression analysis of genes previously reported to be differentially expressed between PCNSL and systemic DLBCL. Rubenstein et al 14 have described 462 ESTs to be differentially expressed between PCNSL and systemic DLBCL with 29 genes to discriminate most significantly. A total of 133 tags of these ESTs were represented on the HG-U95Av2 microarray.…”

Section: Discussionmentioning

confidence: 99%

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Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell

et al. 2007

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To characterize the molecular origin of primary lymphomas of the central nervous system (PCNSL), 21 PCNSLs of immunocompetent patients were investigated by microarray-based gene expression profiling. Comparison of the transcriptional profile of PCNSL with various normal and neoplastic B-cell subsets demonstrated PCNSL (i) to display gene expression patterns most closely related to late germinal center B cells, (ii) to display a gene expression profile similar to systemic diffuse large B-cell lymphomas (DLBCLs) and (iii) to be in part assigned to the activated B-cell-like (ABC) or the germinal center B-cell-like (GCB) subtype of DLBCL.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell

et al. 2007

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“…27 Some studies have suggested that patients who harbor such abnormalities have a shorter overall survival. 23,25 In our study, despite the apparent trend toward shorter survival in these patients, the difference was not statistically significant. The lack of statistical significance may be related to the small number of our patient sample.…”

Section: Discussioncontrasting

confidence: 74%

“…[23][24][25] Interestingly, both in our study and in earlier reports, the majority of primary central nervous system lymphomas show strong expression of Bcl-2 and C-MYC, indicating that overexpression at protein and mRNA levels is poorly correlated with the rearrangements of BCL2 and C-MYC genes. 25,26 Thirty-three percent (7/21) of cases showed additional signals for IGH, BCL2, and C-MYC. These most likely represent additional gene copies due to trisomy or tetrasomy; however, the rearrangement to an unknown partner cannot be entirely excluded.…”

Section: Discussionsupporting

confidence: 58%

Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases

et al. 2010

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Primary central nervous system lymphomas are rare neoplasms characterized by a dismal prognosis relative to other extranodal lymphomas. Approximately 98% of primary central nervous system lymphomas are of B-cell origin, and most belong to the diffuse large B-cell type. Recently, diffuse large B-cell lymphomas have been subcategorized into germinal center and nongerminal center types based on gene expression profiles and immunohistochemical expression of CD10, Bcl-6, and MUM1. Studies have shown that the overall survival rate of the germinal center group is better than that of the nongerminal center lymphomas. In this study, 31 cases of primary central nervous system lymphomas of the diffuse large B-cell type were retrieved, reviewed, and immunostained for CD10, Bcl-6, MUM1, and Ki-67. Subclassification was carried out as described earlier, where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered characteristic of germinal center subtype and the opposite expression of nongerminal center subtype. Furthermore, the proliferative activity was semiquantitatively assessed using percent positive cells staining with Ki-67. Of the 31 cases examined, 26 (84%) were found to belong to the nongerminal center type. The Ki-67 index in these 26 cases ranged from 30 to 90% (mean, 69%). Five cases were categorized as the germinal center subtype. They had an Ki-67 index between 70 and 90% (mean, 78%). Interestingly, none of our patients were known to be HIV positive. One patient had a 10-year history of orthotopic liver transplant. We also performed fluorescence in situ hybridization analysis on formalin-fixed material and found that 38% of the cases where tissue was available had abnormalities of MYC/ IGH and/or IGH/BCL2. We conclude that most primary central nervous system diffuse large B-cell lymphomas are of the nongerminal center origin. Regardless of the germinal center status, all cases showed a high proliferative rate. A statistically significant difference in the overall survival between the two groups was not seen.

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