ELEVATED FREQUENCY OF MICROSATELLITE MUTATIONS IN TK6 HUMAN LYMPHOBLAST CLONES SELECTED FOR MUTATIONS AT THE THYMIDINE KINASE LOCUS

被引:22
作者
LI, CY
YANDELL, DW
LITTLE, JB
机构
[1] HARVARD UNIV, SCH PUBL HLTH, RADIOBIOL LAB, BOSTON, MA 02115 USA
[2] UNIV VERMONT, DEPT PATHOL, BURLINGTON, VT 05405 USA
关键词
D O I
10.1128/MCB.14.7.4373
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A major question in carcinogenesis is, How can a normal cell accumulate multiple mutations in different genes on different chromosomes, when the mutation rate of each gene is in the range of 10(-8) to 10(-5) per cell division? We hypothesize that many mutations may not be isolated events but rather are accompanied by concomitant mutations elsewhere in the genome. To test this hypothesis, 331 independent clones selected for new mutations at the thymidine kinase (TK) locus on chromosome 17q, and 243 nonselected control clones were examined for mutations in 12 random microsatellite loci dispersed throughout the genome. A total of 24 second-site mutations were identified in the TK mutant clones, compared with 3 in the control clones not selected for mutations at TK. The mutations include small deletions, insertions, and loss of heterozygosity. These results provide evidence that a global trans-acting mutagenic process exists in human cells. The activation of this process could be responsible for causing multiple essential mutations in tumor cells.
引用
收藏
页码:4373 / 4379
页数:7
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