title: Pathway analysis of primary central nervous system lymphoma.
abstract: Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B-cell 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.
authors.affiliation: Department of Hematology and Oncology, Mayo Clinic Jacksonville, FL 32224, USA. Tun.Han@mayo.edu
authors.forename: Han W
authors.initials: HW
authors.lastname: Tun
authors.forename: David
authors.initials: D
authors.lastname: Personett
authors.forename: Karen A
authors.initials: KA
authors.lastname: Baskerville
authors.forename: David M
authors.initials: DM
authors.lastname: Menke
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jaeckle
authors.forename: Pamela
authors.initials: P
authors.lastname: Kreinest
authors.forename: Brandy
authors.initials: B
authors.lastname: Edenfield
authors.forename: Abba C
authors.initials: AC
authors.lastname: Zubair
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Neill
authors.forename: Weil R
authors.initials: WR
authors.lastname: Lai
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: McKinney
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012984:Software