TY - JOUR
T1 - Msh6 protects mature B cells from lymphoma by preserving genomic stability
AU - Peled, Jonathan U.
AU - Sellers, Rani S.
AU - Iglesias-Ussel, Maria D.
AU - Shin, Dong Mi
AU - Montagna, Cristina
AU - Zhao, Chunfang
AU - Li, Ziqiang
AU - Edelmann, Winfried
AU - Morse, Herbert C.
AU - Scharff, Matthew D.
N1 - Funding Information:
Supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (D.-M.S. and H.C.M.) and in part by the National Cancer Institute (award P30CA013330 to R.S.S. and C.M.). J.U.P. is supported by the Medical Scientist Training Program at Albert Einstein College of Medicine (grant T32-GM007288 ). M.D.S. is supported by grants R01-CA72649 and R01-CA102705 and by the Harry Eagle Chair provided by the National Women's Division of the Albert Einstein College of Medicine. W.E. is supported by grants R01-CA76329 and R01-CA93484 .
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
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U2 - 10.2353/ajpath.2010.100234
DO - 10.2353/ajpath.2010.100234
M3 - Article
C2 - 20934970
AN - SCOPUS:78149311127
SN - 0002-9440
VL - 177
SP - 2597
EP - 2608
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -