Msh6 protects mature B cells from lymphoma by preserving genomic stability.


Journal Article

Most human B-cell non-Hodgkin's lymphomas arise from germinal centers. Within these sites, the mismatch repair factor MSH6 participates in antibody diversification. Reminiscent of the neoplasms arising in patients with Lynch syndrome III, mice deficient in MSH6 die prematurely of lymphoma. In this study, we characterized the B-cell tumors in MSH6-deficient mice and describe their histological, immunohistochemical, and molecular features, which include moderate microsatellite instability. Based on histological markers and gene expression, the tumor cells seem to be at or beyond the germinal center stage. The simultaneous loss of MSH6 and of activation-induced cytidine deaminase did not appreciably affect the survival of these animals, suggesting that these germinal center-like tumors arose by an activation-induced cytidine deaminase-independent pathway. We conclude that MSH6 protects B cells from neoplastic transformation by preserving genomic stability.

Full Text

Duke Authors

Cited Authors

  • Peled, JU; Sellers, RS; Iglesias-Ussel, MD; Shin, D-M; Montagna, C; Zhao, C; Li, Z; Edelmann, W; Morse, HC; Scharff, MD

Published Date

  • November 2010

Published In

Volume / Issue

  • 177 / 5

Start / End Page

  • 2597 - 2608

PubMed ID

  • 20934970

Pubmed Central ID

  • 20934970

Electronic International Standard Serial Number (EISSN)

  • 1525-2191

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.2353/ajpath.2010.100234


  • eng