Microsatellite instability at tetranucleotide repeats in skin and bladder cancer
Microsatellite instability at tetranucleotide repeats in skin and bladder cancer
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DOI：
10.1038/sj.onc.1205619
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发表时间：
2002-07-25
期刊：
影响因子：
8
通讯作者：
Kelsey, KT
中科院分区：
文献类型：
--
作者：
Danaee, H;Nelson, HH;Kelsey, KT
最近，一种新形式的 MSI 被描述为仅发生在四核苷酸重复标记处。这被称为选定四核苷酸重复序列的微卫星不稳定性升高（EMAAST）。 EMAST 与 p53 基因的改变以及重复序列的性质有关。我们最初在一系列 61 个非黑色素瘤皮肤癌 (NMSC) 肿瘤中测试了 p53 和修补 (ptch) 基因杂合性丢失 (LOH) 是否与 EMAAST 相关。然后，我们分析了一系列 57 例原发性膀胱癌中 EMAAST 的存在，测试这是否与 p53 基因的突变或表达有关。在 NMSC 和膀胱肿瘤中，我们发现 EMAST 的患病率很高（75.4% 和 43.9%）。在 NMSC 中，具有 p53 或 ptch LOH 的肿瘤中 EMAAST 的患病率较高，但差异不具有统计学意义。在膀胱癌肿瘤中，广泛的 EMAT（三个或更多位点）与 p53 突变存在显着相关性，但没有迹象表明在无突变的 p53 染色异常的肿瘤中 EMAST 升高。 EMAAST 与 p53 突变的关联仅限于非侵袭性疾病。因此，EMAST 可能反映了与 p53 突变相互作用的体细胞事件的特定模式，尤其常见于皮肤癌，仅限于膀胱癌的非侵袭性疾病。
Recently, a novel form of MSI has been described that occurs only at tetranucleotide repeat markers. This has been termed elevated microsatellite instability at selected tetranucleotide repeats (EMAST). EMAST has been related to alterations of the p53 gene, and to the nature of the repeat sequence. We initially tested whether loss of heterozygosity (LOH) at the p53 and the patched (ptch) genes was related to EMAST in a series of 61 non-melanoma skin cancer (NMSC) tumors. We then analysed a series of 57 primary bladder cancers for the presence of EMAST, testing whether this was related to mutation or expression of the p53 gene. In both NMSC and bladder tumors we found a high prevalence of EMAST (75.4 and 43.9%). In NMSC the prevalence of EMAST was higher in tumors that had either p53 or ptch LOH, although the difference was not statistically significant. There was a significant association of extensive EMAST (three or more loci) with mutations in p53 among the bladder cancer tumors, but no indication of elevated EMAST in tumors with abnormal p53 staining without mutation. The association of EMAST with p53 mutation was confined to non-invasive disease. Hence, EMAST likely reflects a particular pattern of somatic events that are interactive with p53 mutation, particularly common in skin cancer and limited to non-invasive disease in bladder cancer.