Msh2-dependent DNA repair mitigates a unique susceptibility of B cell progenitors to c-Myc-induced lymphomas

Rajeev M. Nepal, Li Tong, Blerta Kolaj, Winfried Edelmann, Alberto Martin

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

C-Myc is one of the most common targets of genetic alterations in human cancers. Although overexpression of c-Myc in the B cell compartment predisposes to lymphomas, secondary mutations are required for disease manifestation. In this article, we show that genetic deficiencies causing arrested B cell development and accumulation of B cell progenitors lead to accelerated lymphomagenesis in Eμ c-myc transgenic mice. This result suggests that B cell progenitors are more prone than their mature counterparts to developing secondary oncogenic lesions that complement c-Myc in promoting transformation. To investigate the nature of these oncogenic lesions, we examined Eμ c-myc mice deficient in mismatch repair function. We report that Msh2 G674A/G674A Eμ c-myc and Msh2G674A/G674A Eμ c-myc mice rapidly succumb to pro-B cell stage lymphomas, indicating that Msh2-dependent mismatch repair function actively suppresses c-Myc-associated oncogenesis during early B cell development.

Original languageEnglish (US)
Pages (from-to)18698-18703
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number44
DOIs
Publication statusPublished - Nov 3 2009

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Keywords

  • Apoptosis
  • Mismatch repair
  • Oncogenesis
  • p53

ASJC Scopus subject areas

  • General

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