Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.
Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.
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DOI：
10.1038/sj.bjc.6600111
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发表时间：
2002-02-12
影响因子：
8.8
通讯作者：
Martinsson, T
中科院分区：
文献类型：
--
作者：
Abel, F;Sjoberg, R-M;Ejeskar, K;Krona, C;Martinsson, T
编码Caspase-9和DFF 45的基因最近都被定位到染色体区域1p36.2，这是一个据称涉及神经母细胞瘤肿瘤中一个或几个肿瘤抑制基因的区域。这项研究提出了一个更新的重叠群的'最小区域重叠的缺失'在斯堪的纳维亚神经母细胞瘤肿瘤，并建议DFF 45是本地化的区域。人类DFF 45基因的基因组组织，推导出的DNA序列的计算机比较，本文首次描述。在本研究中，通过分析基因的基因组序列筛选了44个原发性肿瘤的突变。在44个肿瘤中的两个中，在DFFA基因中检测到一种罕见的等位基因变体，该变体导致DFF 45的保留疏水斑块中的非极性至极性氨基酸交换。1例为半合子，由于删除了更常见的等位基因的多态性。在194个正常对照等位基因中，只有一个被发现携带这种变异等位基因，因此在97个健康对照个体中没有一个是纯合子。此外，我们的RT-PCR表达研究表明，DFF 45优选在低阶段神经母细胞瘤肿瘤中表达，在高阶段神经母细胞瘤中表达程度较低。我们的结论是，虽然编码突变的Caspase-9和DFF 45是罕见的神经母细胞瘤肿瘤，我们发现一个罕见的等位基因在两个神经母细胞瘤的情况下，应采取保证进一步研究DFF 45在神经母细胞瘤遗传学中的作用。英国癌症杂志（2002）86，596-604。DOI：10.1038/sj/bjc/6600111 www.bjcancer.com © 2002英国癌症研究中心
The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the ‘Smallest Region of Overlap of deletions’ in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT–PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics. British Journal of Cancer (2002) 86, 596–604. DOI: 10.1038/sj/bjc/6600111 www.bjcancer.com © 2002 Cancer Research UK