Candidate target genes for loss of heterozygosity on human chromosome 17q21
Candidate target genes for loss of heterozygosity on human chromosome 17q21
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DOI：
10.1038/sj.bjc.6601848
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发表时间：
2004-06-14
影响因子：
8.8
通讯作者：
Callahan, R
中科院分区：
文献类型：
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作者：
DeMarchis, L;Cropp, C;Callahan, R
17q21染色体杂合性缺失（LOH）在30%的原发性乳腺肿瘤中被检测到。最小的共同区域缺失发生在D17S746和D17S846多态性序列标记位点之间的间隔，分别位于染色体17q21的两个重组p1噬菌体克隆：122F4和50H1上。为了确定LOH的靶基因，我们定义了这一染色体区域的图谱。我们发现以下基因：JUP， FK506BP10, SC65, Gastrin （GAS）和HAP1。在本研究中已鉴定的基因中，只有JUP位于D17S746和D17S846之间。这是一个有趣的发现，因为早期的研究表明，JUP在乳腺、肺和甲状腺肿瘤以及染色体17q21上有LOH的细胞系中的表达发生了改变。然而，使用在17q21处LOH的原发性乳腺肿瘤dna的单链构象多态性分析，在JUP中未检测到突变。我们没有发现JUP的转录启动子在17q21处LOH的肿瘤dna中甲基化的证据。我们推测，原发性乳腺肿瘤中LOH的靶基因位于染色体17q21上，要么是JUP，导致单倍性表达不足，要么可能是位于D17S846和JUP之间的一个未知基因。
Loss of heterozygosity (LOH) on chromosome 17q21 has been detected in 30% of primary human breast tumours. The smallest common region deleted occurred in an interval between the D17S746 and D17S846 polymorphic sequences tagged sites that are located on two recombinant P1-bacteriophage clones of chromosome 17q21: 122F4 and 50H1, respectively. To identify the target gene for LOH, we defined a map of this chromosomal region. We found the following genes: JUP, FK506BP10, SC65, Gastrin ( GAS) and HAP1. Of the genes that have been identified in this study, only JUP is located between D17S746 and D17S846. This was of interest since earlier studies have shown that JUP expression is altered in breast, lung and thyroid tumours as well as cell lines having LOH in chromosome 17q21. However, no mutations were detected in JUP using single-strand conformation polymorphism analysis of primary breast tumour DNAs having LOH at 17q21. We could find no evidence that the transcription promoter for JUP is methylated in tumour DNAs having LOH at 17q21. We suspect that the target gene for LOH in primary human breast tumours on chromosome 17q21 is either JUP and results in a haploinsufficiency for expression or may be an unidentified gene located in the interval between D17S846 and JUP.