Microsatellite instability (MSI) increases with age in normal somatic cells

被引:30
作者
Coolbaugh-Murphy, MI
Xu, JP
Ramagli, LS
Brown, BW
Siciliano, MJ
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA
[2] Univ Texas, Hlth Sci Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA
关键词
microsatellite instability; small pool PCR; mismatch repair; HNPCC; aging in normal cells;
D O I
10.1016/j.mad.2005.06.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Small pool PCR (SP-PCR) is a sensitive method for the detection and quantification of microsatellite instability (MSI) in somatic cells. Here we propose that mutant microsatellite fragments accumulate with age in normal somatic cells and tha: this increase in MSI can be quantified by SP-PCR. MSI at 6 microsatellite loci was determined by SP-PCR in PBL DNA from 17 "normal" blood bank donors. These individuals varied in age from 20 to 67 y/o. MSI phenotypes were plotted against age in a regression analysed. A positive slope indicated a correlation between age and MSI phenotype (p = 0.0006). The mean weighted average mutant frequencies across all loci for all individuals in the age groups (0.009 for 20-30 y/o; 0.019 for 35-50 y/o; 0.034 for 60-70 y/o) were also significantly different rom each other (p < 0.01). A baseline for increases of MSI with age in human somatic cells was therefore begun and the effectiveness of SP-PCR to evaluate low, but significant, levels of MSI, established. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:1051 / 1059
页数:9
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