Pathway analysis of primary central nervous system lymphoma

Han W. Tun, David Personett, Karen A. Baskerville, David M. Menke, Kurt Jaeckle, Pamela Kreinest, Brandy Edenfield, Abba C. Zubair, Brian P. O'Neill, Weil R. Lai, Peter J. Park, Michael McKinney

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large Elcell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a "CNS signature." Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true "CNS signature" because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.

Original languageEnglish (US)
Pages (from-to)3200-3210
Number of pages11
JournalBlood
Volume111
Issue number6
DOIs
StatePublished - Mar 15 2008

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Neurology
Lymphoma
Central Nervous System
Extracellular Matrix
Gene expression
Nervous System
B-Lymphocytes
Adhesion
Gene Expression
Genes
Cells
Osteopontin
Tropism
Extracellular Matrix Proteins
Computational Biology
Transcriptome
Cell Movement
Bioinformatics
Immunohistochemistry
Genome

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Tun, H. W., Personett, D., Baskerville, K. A., Menke, D. M., Jaeckle, K., Kreinest, P., ... McKinney, M. (2008). Pathway analysis of primary central nervous system lymphoma. Blood, 111(6), 3200-3210. https://doi.org/10.1182/blood-2007-10-119099
Tun, Han W. ; Personett, David ; Baskerville, Karen A. ; Menke, David M. ; Jaeckle, Kurt ; Kreinest, Pamela ; Edenfield, Brandy ; Zubair, Abba C. ; O'Neill, Brian P. ; Lai, Weil R. ; Park, Peter J. ; McKinney, Michael. / Pathway analysis of primary central nervous system lymphoma. In: Blood. 2008 ; Vol. 111, No. 6. pp. 3200-3210.
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abstract = "Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large Elcell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a {"}CNS signature.{"} Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true {"}CNS signature{"} because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.",
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Tun, HW, Personett, D, Baskerville, KA, Menke, DM, Jaeckle, K, Kreinest, P, Edenfield, B, Zubair, AC, O'Neill, BP, Lai, WR, Park, PJ & McKinney, M 2008, 'Pathway analysis of primary central nervous system lymphoma', Blood, vol. 111, no. 6, pp. 3200-3210. https://doi.org/10.1182/blood-2007-10-119099

Pathway analysis of primary central nervous system lymphoma. / Tun, Han W.; Personett, David; Baskerville, Karen A.; Menke, David M.; Jaeckle, Kurt; Kreinest, Pamela; Edenfield, Brandy; Zubair, Abba C.; O'Neill, Brian P.; Lai, Weil R.; Park, Peter J.; McKinney, Michael.

In: Blood, Vol. 111, No. 6, 15.03.2008, p. 3200-3210.

Research output: Contribution to journalArticle

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AU - Tun, Han W.

AU - Personett, David

AU - Baskerville, Karen A.

AU - Menke, David M.

AU - Jaeckle, Kurt

AU - Kreinest, Pamela

AU - Edenfield, Brandy

AU - Zubair, Abba C.

AU - O'Neill, Brian P.

AU - Lai, Weil R.

AU - Park, Peter J.

AU - McKinney, Michael

PY - 2008/3/15

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N2 - Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large Elcell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a "CNS signature." Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true "CNS signature" because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.

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Tun HW, Personett D, Baskerville KA, Menke DM, Jaeckle K, Kreinest P et al. Pathway analysis of primary central nervous system lymphoma. Blood. 2008 Mar 15;111(6):3200-3210. https://doi.org/10.1182/blood-2007-10-119099