Increased expression of germinal center-associated nuclear protein RNA-primase is associated with lymphomagenesis

Satoru Fujimura, Yan Xing, Motohiro Takeya, Yasuyuki Yamashita, Koichi Ohshima, Kazuhiko Kuwahara, Nobuo Sakaguchi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Lymphomas arise containing abnormalities of various differentiation stage-specific molecules. In the study reported here, we have shown abnormal up-regulation of germinal center B cell-associated GANP in various human lymphomas including mantle cell, diffuse large B cell, and Hodgkin lymphoma, by immunohistochemical analysis. To study the role of GANP in lymphomagenesis, we generated mutant mice (ganp-Tg) that express the transgenic ganp gene under immunoglobulin enhancer and promoter control. Ganp-Tg mice showed a high incidence of lymphomagenesis (29.5%) after aging with a non-B/non-T cell surface phenotype having slight CD45R/B220 expression and Ig transcripts of rearranged VH-DH-JH IgH loci. Lymphomas generated in ganp-Tg mice displayed similar pathologic characteristics to mouse reticulum cell neoplasm or Hodgkin lymphoma-like lesions. The VH sequences of individual mice showed that the tumors proliferated from a single clone or oligoclones, as is found in human diffuse large B-cell lymphomas and Hodgkin lymphoma. These results suggest that GANP overexpression is a causative factor in the generation of B lymphomas.

Original languageEnglish
Pages (from-to)5925-5934
Number of pages10
JournalCancer Research
Volume65
Issue number13
DOIs
Publication statusPublished - 01-07-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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