title: Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma.
abstract: Of the genetic changes in primary central nervous system lymphoma (PCNSL), little is known. To detect copy number alterations and differentially expressed genes in PCNSL, we analyzed a total of 12 PCNSL samples with high-resolution array-based comparative genomic hybridization and performed expression profiling in 7 of the 12 samples. The most frequent deletion found in 8 patients (66.7%) occurred in 9p21.3 containing CDKN2A. We compiled the top 96 genes (family-wise error rate, P < .05) showing the greatest differential expression between PCNSL and normal lymph node tissues. From these, we selected 8 candidate genes (NPFFR2, C4orf7, OSMR, EMCN, TPO, FNDC1, COL12A1, and MSC) in which expression changes were associated with copy number aberrations. All 8 genes showed both down-regulation in expression microarray and deletion in array-based comparative genomic hybridization analyses. These genes participate in cell signaling or cell adhesion. In addition, low mRNA expression of C4orf7 was significantly associated with poor survival (P = .0425). Using gene set enrichment analysis, we identified several signal transduction pathways, such as Janus kinase-signal transducers and activators of transcription pathway and adhesion-related pathways, which may be involved in pathogenesis of PCNSL. In conclusion, this study identified novel tumor suppressor genes that may serve as therapeutic targets of PCNSL.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Seoul, South Korea.
authors.forename: Chang Ohk
authors.initials: CO
authors.lastname: Sung
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Sivasundaram
authors.initials: S
authors.lastname: Karnan
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.forename: Yeon-Lim
authors.initials: YL
authors.lastname: Suh
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.forename: Young-Hyeh
authors.initials: YH
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods*; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054928:Validation Studies as Topic