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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. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-10-119099v1 111/6/3200    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tun, H. W. Articles by McKinney, M. Search for Related Content PubMed PubMed Citation Articles by Tun, H. W. Articles by McKinney, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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