Homozygous deletion of INK4a/ARF genes and overexpression of bcl-2 in relation with poor prognosis in immunocompetent patients with primary central nervous system lymphoma of the diffuse large B-cell type

Y. Hayashi, M. Iwato, Y. Arakawa, H. Fujisawa, Y. Thoma, M. Hasegawa, O. Tachibana, J. Yamashita

研究成果: ジャーナルへの寄稿学術論文査読

23 被引用数 (Scopus)

抄録

Only a few reports have been published on molecular genetic alterations in primary central nervous system lymphomas (PCNSLs) of the diffuse large B-cell type and no reports have addressed the correlation between the genetic alterations and clinical course of the patients with this neoplasm. Thus, the molecular background of the PCNSL and its importance of the clinical course of the patients are still unclear. We investigated a series of 14 patients with PCNSL to determine structural alterations of the INK4a/ARF, MDM2, and TP53 genes, the status of bcl-2 and bcl-6 protein expression, and the clinical course of the patients (i.e. their survival time after diagnosis). No structural alterations of MDM2 and TP53 genes were found. Only INK4a/ARF genes whose expression affects both the p16INK4a-Rb and p14ARF-mdm2-p53 pathways in the regulation for cell cycle and apoptosis, showed an alteration of the homozygous deletions at a high frequency (nine of 14 patients: 64%). This specific alteration was not related with the bcl-6 expression, but a relation was shown with overexpression of the bcl-2 anti-apoptotic protein (p = 0.036, chi-square test), as well as a shorter patient survival (p = 0.044, Wilcoxon test). There was only a tendency, not a significant correlation, in which the patients with bcl-2 overexpression resulted in poor prognosis (p = 0.149). The present study is the first to suggest that the INK4a/ARF gene homozygous deletions and overexpression of the bcl-2 protein may be correlated with each other and together serve as important predictors for the prognosis of patients with PCNSL.

本文言語英語
ページ(範囲)51-58
ページ数8
ジャーナルJournal of Neuro-Oncology
55
1
DOI
出版ステータス出版済み - 2001

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 神経学
  • 臨床神経学
  • 癌研究

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