Panzer S, Kuhl D P, Caskey C T
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Stem Cells. 1995 Mar;13(2):146-57. doi: 10.1002/stem.5530130206.
Numerous mutations have been related to various types of cancer. Short tandem repeats (STRs) are repetitive DNA elements that are often polymorphic in normal populations. Triplet repeat expansion has been related pathogenetically to six diseases: fragile X syndrome, fragile X E syndrome, spinobulbar muscular atrophy, myotonic dystrophy, Huntington's disease, and spinocerebellar ataxia type 1. The characteristics of the GC-rich repeat expansion are diverse and result in profound changes in phenotype, sometimes within a single generation in affected families. We expect that simple repeat expansion will cause some cancers based on our knowledge of these unstable DNA sequences in the previously mentioned genes. This may occur by alteration of tumor suppressor gene expression, alteration in coding features of proteins, or change in bystander oncogene expression such as that which occurs with DNA methylation. The demonstrated meiotic instability could link this mechanism of mutation of familial cancer syndromes. The recent discovery of STR instability at multiple sites in hereditary nonpolyposis colon cancer suggests sequence instability may be a factor in cancer progression. Continued identification of candidate genes containing triplet repeats should allow a ready testing of the hypothesis that unstable simple repeat sequences can cause cancer.
众多突变已与各类癌症相关。短串联重复序列（STRs）是重复性DNA元件，在正常人群中通常具有多态性。三联体重复序列扩增在发病机制上已与六种疾病相关：脆性X综合征、脆性X E综合征、脊髓延髓肌肉萎缩症、强直性肌营养不良症、亨廷顿舞蹈症以及1型脊髓小脑共济失调症。富含GC的重复序列扩增的特征多样，会导致表型发生深刻变化，在受影响的家族中有时在一代之内就会出现这种情况。基于我们对上述基因中这些不稳定DNA序列的了解，我们预计简单重复序列扩增会引发某些癌症。这可能通过改变肿瘤抑制基因表达、改变蛋白质编码特征或改变旁观者癌基因表达（如DNA甲基化时发生的情况）而发生。已证实的减数分裂不稳定性可能与家族性癌症综合征的这种突变机制相关。最近在遗传性非息肉病性结肠癌的多个位点发现STR不稳定性，表明序列不稳定性可能是癌症进展的一个因素。持续鉴定含有三联体重复序列的候选基因应能随时检验不稳定简单重复序列可引发癌症这一假说。
