Judson H, van Roy N, Strain L, Vandesompele J, Van Gele M, Speleman F, Bonthron D T
Molecular Medicine Unit, University of Leeds, St James's University Hospital, UK.
Hum Genet. 2000 Apr;106(4):406-13. doi: 10.1007/s004390000257.
We have characterised the DFFB gene, encoding the active subunit of the apoptotic nuclease DNA fragmentation factor (DFF40). DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73. The DFFA gene (encoding the inhibitory DFF45 subunit) also maps to 1p36.2-36.3, and we show by FISH that DFFB lies distal to DFFA. We have also mapped a processed DFFB pseudogene to chromosome 9. DFFB itself has seven coding exons spanning 10 kb. Exhaustive mutation screening of 41 neuroblastomas and other tumours in which a 1p36 tumour suppressor gene is implicated showed no tumour-specific mutations. A coding region polymorphism was used to demonstrate uniformly biallelic expression in human fetal DFFB transcripts. Since the putative neuroblastoma tumour suppressor gene in distal 1p36 is predicted to be maternally expressed, the lack of imprinting and absence of somatic mutations in DFFB indicate that it is probably not the neuroblastoma tumour suppressor gene.
我们已对编码凋亡核酸酶DNA片段化因子（DFF40）活性亚基的DFFB基因进行了特征分析。DFFB定位于1p36，靠近印记的假定肿瘤抑制基因TP73。DFFA基因（编码抑制性DFF45亚基）也定位于1p36.2 - 36.3，并且我们通过荧光原位杂交显示DFFB位于DFFA的远端。我们还将一个加工后的DFFB假基因定位于9号染色体。DFFB本身有7个编码外显子，跨度为10 kb。对41例神经母细胞瘤和其他涉及1p36肿瘤抑制基因的肿瘤进行详尽的突变筛查，未发现肿瘤特异性突变。利用一个编码区多态性来证明人胎儿DFFB转录本中双等位基因的一致表达。由于预计1p36远端的假定神经母细胞瘤肿瘤抑制基因是母系表达的，DFFB缺乏印记且不存在体细胞突变表明它可能不是神经母细胞瘤肿瘤抑制基因。
