SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma.
SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma.
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DOI：
10.1038/sj.bjc.6601447
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发表时间：
2004-01-26
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
3p21.3 RASSF1A肿瘤抑制基因（TSG）提供了TSG因启动子甲基化而非体细胞突变而失活的范例。最近，我们在肺癌和乳腺癌中发现了频繁的启动子甲基化，但没有SLIT2的体细胞突变，这表明SLIT2和RASSF1A TSGs之间存在相似性。RASSF1A的表观遗传失活首先在肺癌和乳腺癌中被描述，随后在广泛的人类癌症中被描述，包括神经母细胞瘤、肾母细胞瘤和肾细胞癌（RCC）。这些发现促使我们研究SLIT2甲基化在这三种人类癌症中的作用。我们分析了49例神经母细胞瘤（NBs）、37例Wilms肿瘤和48例RCC，并在29%的NB、38%的Wilms肿瘤和25%的RCC中检测到SLIT2启动子甲基化。之前，我们已经在相同的肿瘤系列中发现了频繁的RASSF1A甲基化，在NB和Wilms的肿瘤样本中发现了频繁的CASP8甲基化。然而，在NB和RCC中，SLIT2启动子甲基化与RASSF1A或CASP8甲基化之间没有显著关联。在Wilms肿瘤中，RASSF1A和SLIT2甲基化之间有负相关的趋势，尽管这没有达到统计学意义。在分析的肿瘤中，未发现SLIT2启动子甲基化与特定临床病理特征之间的关联。这些发现暗示SLIT2启动子甲基化在儿童和成人癌症的发病机制中都起作用，并建议进一步研究SLIT2在其他肿瘤类型中的作用。然而，在所分析的肿瘤类型中，SLIT2的表观遗传失活频率低于RASSF1A。
The 3p21.3 RASSF1A tumour suppressor gene (TSG) provides a paradigm for TSGs inactivated by promoter methylation rather than somatic mutations. Recently, we identified frequent promoter methylation without somatic mutations of SLIT2 in lung and breast cancers, suggesting similarities between SLIT2 and RASSF1A TSGs. Epigenetic inactivation of RASSF1A was first described in lung and breast cancers and subsequently in a wide range of human cancers including neuroblastoma, Wilms' tumour and renal cell carcinoma (RCC). These findings prompted us to investigate SLIT2 methylation in these three human cancers. We analysed 49 neuroblastomas (NBs), 37 Wilms' tumours and 48 RCC, and detected SLIT2 promoter methylation in 29% of NB, 38% of Wilms' tumours and 25% of RCC. Previously, we had demonstrated frequent RASSF1A methylation in the same tumour series and frequent CASP8 methylation in the NB and Wilms' tumour samples. However, there was no significant association between SLIT2 promoter methylation and RASSF1A or CASP8 methylation in NB and RCC. In Wilms' tumour, there was a trend for a negative association between RASSF1A and SLIT2 methylation, although this did not reach statistical significance. No associations were detected between SLIT2 promoter methylation and specific clinicopathological features in the tumours analysed. These findings implicate SLIT2 promoter methylation in the pathogenesis of both paediatric and adult cancers and suggest that further investigations of SLIT2 in other tumour types should be pursued. However, epigenetic inactivation of SLIT2 is less frequent than RASSF1A in the tumour types analysed.
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影响因子：
64.5
作者：
Brose, K;Bland, KS;Kidd, T
通讯作者：
Kidd, T
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
8
作者：
Astuti, D;Agathanggelou, A;Latif, F
通讯作者：
Latif, F
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
8
作者：
Dallol, A;Forgacs, E;Latif, F
通讯作者：
Latif, F