Genetic and epigenetic changes in the common 1p36 deletion in neuroblastoma tumours.
Genetic and epigenetic changes in the common 1p36 deletion in neuroblastoma tumours.
复制标题
神经母细胞瘤肿瘤中常见1P36缺失的遗传和表观遗传变化。
DOI：
10.1038/sj.bjc.6604032
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发表时间：
2007-11-19
影响因子：
8.8
通讯作者：
Martinsson, T
中科院分区：
文献类型：
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作者：
Caren, H;Fransson, S;Ejeskar, K;Kogner, P;Martinsson, T
在神经母细胞瘤(NB)肿瘤中，染色体1p经常缺失。由于不同研究小组进行的杂合性丧失研究，通常缺失的区域已经缩小。基于早期的定位数据，我们聚焦于1p36(chr1：7 765 595-11 019 814)上的一个区域，通过探索表观遗传调控特征，即DNA甲基化和组蛋白去乙酰化，DNA水平的突变和 的表达，对30个基因进行了分析。用组蛋白去乙酰化酶抑制剂Trichostatin A处理NB细胞后，30个基因中的4个基因ERRFI1(MIG-6)、PIK3CD、RBP7(CRBPIV)和CASZ1的转录增加，表明这些基因可能受到NBS表观遗传下调的影响。检测到2例PIK3CD基因非同义突变。1例患者在同一外显子中存在三种变异，pR188W。另一例患者存在p.M655I变异。此外，还发现了同义变异和内含子序列中的一个变异。与有利的NBS相比，该基因的mRNA表达在不利的NBS中下调。在ERRFI1基因p.N343S中也发现了一个非同义突变和一个同义突变。上述变异在健康对照组中均未发现。总之，在分析的30个基因中，PIK3CD基因是最有兴趣进一步研究NB发育和进展的基因之一。
Chromosome 1p is frequently deleted in neuroblastoma (NB) tumours. The commonly deleted region has been narrowed down by loss of heterozygosity studies undertaken by different groups. Based on earlier mapping data, we have focused on a region on 1p36 (chr1: 7 765 595–11 019 814) and performed an analysis of 30 genes by exploring features such as epigenetic regulation, that is DNA methylation and histone deacetylation, mutations at the DNA level and mRNA expression. Treatment of NB cell lines with the histone deacetylase inhibitor trichostatin A led to increased gene transcription of four of the 30 genes, ERRFI1 (MIG-6), PIK3CD, RBP7 (CRBPIV) and CASZ1, indicating that these genes could be affected by epigenetic downregulation in NBs. Two patients with nonsynonymous mutations in the PIK3CD gene were detected. One patient harboured three variations in the same exon, and p.R188W. The other patient had the variation p.M655I. In addition, synonymous variations and one variation in an intronic sequence were also found. The mRNA expression of this gene is downregulated in unfavourable, compared to favourable, NBs. One nonsynonymous mutation was also identified in the ERRFI1 gene, p.N343S, and one synonymous. None of the variations above were found in healthy control individuals. In conclusion, of the 30 genes analysed, the PIK3CD gene stands out as one of the most interesting for further studies of NB development and progression.