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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3200-3210.
Prepublished online as a Blood First Edition Paper on January 9, 2008; DOI 10.1182/blood-2007-10-119099.
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Submitted October 22, 2007
Accepted December 31, 2007
Pathway analysis of primary central nervous system lymphoma
Han W. Tun*, David Personett, Karen A Baskerville, David M Menke, Kurt A Jaeckle, Pamela Kreinest, Brandy Edenfield, Abba C Zubair, Brian P O'Neill, Weil R Lai, Peter J Park, and Michael McKinney
Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL
Department of Molecular Pharmacology and Therapeutics, Mayo Clinic, Jacksonville, FL
Department of Pathology, Mayo Clinic, Jacksonville, FL
Department of Neurology, Mayo Clinic, Jacksonville, FL
Department of Cancer Biology, Mayo Clinic, Jacksonville, FL
Department of Neurology, Mayo Clinic, Rochester, MN
Harvard-Partners Center for Genetics and Genomics, Boston, MA
* Corresponding author; email: tun.han{at}mayo.edu.
Primary CNS lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the CNS. We performed a genome-wide gene expression comparison between PCNSL and nonCNS DLBCL, 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 upregulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells is demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biological 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" since we contrasted PCNSL with wide-spectrum nonCNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.
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