4.7 Article

Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma

Journal

BLOOD
Volume 117, Issue 4, Pages 1291-1300

Publisher

AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-07-297861

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Funding

  1. Samsung Biomedical Research Institute [SBRI C-A8-202]
  2. Korea Healthcare Technology RD Project
  3. Ministry for Health & Welfare, Republic of Korea [A092255]
  4. Grants-in-Aid for Scientific Research [22700888] Funding Source: KAKEN

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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. (Blood. 2011; 117(4): 1291-1300)

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