Baross-Francis A, Milhausen M K, Andrew S E, Jevon G, Jirik F R
Centre for Molecular Medicine and Therapeutics, Department of Medicine, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Carcinogenesis. 2000 Jun;21(6):1259-62.
We reported previously that thymic lymphomas arising in mice lacking the DNA mismatch repair (MMR) gene, Msh2(-/-), exhibited striking elevations in the mutation frequency of a transgenic lacI reporter gene when compared with normal Msh2(-/-) tissues. To investigate whether hypermutation was a feature of all tumors arising in MMR-deficient mice, lacI transgene mutation frequencies were obtained from several different mouse tumors deficient for PMS2 and/or MSH2. While lacI gene hypermutation was again clearly evident in Msh2 +/- ms2(-/-) and Msh2(-/-)Pms2(-/-) thymic lymphomas, three non-thymic MSH2-deficient tumors failed to show lacI gene mutation frequency elevations when compared with a normal tissue of MMR-deficient mice. The elevated mutation frequencies in the lymphoid tumors, and the finding of multiple clustered mutations in lacI genes rescued from these tumors, suggest that they are possibly generated by a lymphoma-specific hypermutational mechanism.
我们之前报道过，与正常的Msh2(-/-)组织相比，在缺乏DNA错配修复（MMR）基因Msh2的小鼠中产生的胸腺淋巴瘤，其转基因lacI报告基因的突变频率显著升高。为了研究高突变是否是MMR缺陷小鼠中所有肿瘤的特征，我们从几种不同的PMS2和/或MSH2缺陷的小鼠肿瘤中获得了lacI转基因突变频率。虽然在Msh2+/-Msh2(-/-)和Msh2(-/-)Pms2(-/-)胸腺淋巴瘤中，lacI基因高突变再次明显可见，但与MMR缺陷小鼠的正常组织相比，三种非胸腺MSH2缺陷肿瘤未显示lacI基因突变频率升高。淋巴样肿瘤中升高的突变频率，以及从这些肿瘤中拯救出的lacI基因中多个簇状突变的发现，表明它们可能是由淋巴瘤特异性高突变机制产生的。
