Microsatellite instability and its relevance to cutaneous tumorigenesis
Microsatellite instability and its relevance to cutaneous tumorigenesis
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DOI：
10.1034/j.1600-0560.2002.290501.x
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发表时间：
2002-05
影响因子：
1.7
通讯作者：
M. Hussein;G. Wood
中科院分区：
文献类型：
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作者：
M. Hussein;G. Wood
越来越多的证据表明，人类肿瘤会按顺序积累多种突变，而正常细胞的低自发突变率(每个细胞2-3个突变)无法解释这些突变。数学模型估计，要发展实体肿瘤，每个肿瘤细胞需要多达6-12个突变。因此，为了解释如此高的突变率，有人提出肿瘤细胞是遗传不稳定的，即它们在被称为微卫星的短重复DNA序列上存在全基因组范围的突变。微卫星重复序列散布在人类基因组中，主要分布在非编码区，可引起长度增加或减少的变异，即微卫星不稳定性(MSI)。这种不稳定性在越来越多的皮肤肿瘤中被报道，包括：黑素细胞肿瘤、基底细胞癌和原发皮肤T细胞淋巴瘤。此外，在一些遗传性疾病如Muir-Torre综合征、Von Reckinghausen病和播散性浅表性汗孔角化症引起的皮肤肿瘤中也观察到了MSI。虽然其中一些疾病的MSI反映了潜在的DNA复制错误，但其他疾病的不稳定机制仍不清楚。到目前为止，MSI被认为是一种独特的致癌途径，显示出惊人的多功能性。对皮肤肿瘤的影响值得进一步研究。
Increasing evidence suggests that human tumors sequentially accumulate multiple mutations that cannot be explained by the low rates of spontaneous mutations in normal cells (2–3 mutations/cell). The mathematical models estimate that for the solid tumors to develop, as many as 6–12 mutations are required in each tumor cell. Therefore, to account for such high mutation rates, it is proposed that tumor cells are genetically unstable, i.e. they have genome‐wide mutations at short repetitive DNA sequences called microsatellites. Microsatellite repeats are scattered throughout the human genome, primarily in the non‐coding regions, and can give rise to variants with increased or reduced lengths, i.e. microsatellite instability (MSI). This instability has been reported in an increasing number of cutaneous tumors including: melanocytic tumors, basal cell carcinomas and primary cutaneous T‐cell lymphomas. Moreover, MSI has been observed in skin tumors arising in the context of some hereditary disorders such as Muir–Torre syndrome, Von Recklinghausen's disease and disseminated superficial porokeratosis. While MSI in some of these disorders reflects underlying DNA replication errors, the mechanism of instability in others is still unknown. Thus far, MSI is considered to be a distinct tumorigenic pathway that reveals surprising versatility. The ramifications for cutaneous neoplasms warrant further investigation.