Frameshift mutations of RIZ, but no point mutations in RIZ1 exons in malignant melanomas with deletions in 1p36
Frameshift mutations of RIZ, but no point mutations in RIZ1 exons in malignant melanomas with deletions in 1p36
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DOI：
10.1038/sj.onc.1205457
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发表时间：
2002-05-02
期刊：
影响因子：
8
通讯作者：
Woenckhaus, C
中科院分区：
文献类型：
--
作者：
Poetsch, M;Dittberner, T;Woenckhaus, C
最近，视网膜母细胞瘤蛋白相互作用锌指基因RIZ已被提出作为1p36上的肿瘤抑制基因座的候选者，因为RIZ1 RNA在人类肿瘤中常见的丢失。此外，该基因的移码突变已在多种具有微卫星不稳定性的肿瘤中得到证实。由于该区域的改变已被描述为恶性黑色素瘤，我们研究了16个典型痣，19个非典型痣，33个原发性黑色素瘤病变和25个转移瘤的石蜡包埋切片的DNA和DNA从四个黑色素瘤细胞系的PCR和直接测序分析的RIZ。在17%的黑色素瘤样本和8.6%的痣样本中发现了RIZ基因的移码突变，但我们无法证明RIZ1外显子中存在任何错义突变。RIZ基因无洛缺失，6个二核苷酸标记或单核苷酸重复IGRIIR、hMSH3和hMSH6的微卫星不稳定性均未在RIZ移码突变的样本中得到证实。虽然我们的研究结果不能解释在该肿瘤中发现的1p36的高缺失率，但他们认为RIZ在皮肤恶性黑色素瘤的多步骤肿瘤形成过程中具有潜在的作用。
Recently, the retinoblastoma protein interacting zinc finger gene RIZ has been proposed as a candidate for the tumor suppressor locus on 1p36, because of the common loss of RIZ1 RNA in human tumors. In addition, frameshift mutations of this gene have been demonstrated in a variety of tumors with microsatellite instability. Since alterations in this region have been described in malignant melanomas, we investigated DNA of paraffin-em bedded sections from 16 typical naevi, 19 atypical naevi, 33 primary melanoma lesions and 25 metastases and DNA from four melanoma cell lines by PCR and direct sequencing analysis of RIZ. Frameshift mutations in the RIZ gene were found in 17% of melanoma samples and 8.6% of naevi, but we could not demonstrate any missense mutations in the exons of RIZ1. No LOH of the RIZ gene nor any microsatellite instability in six dinucleotide markers or in the mononucleotide repeats IGRIIR, hMSH3, and hMSH6 could be demonstrated in the samples with RIZ frameshift mutations. Although our results do not explain the high rate of deletions in 1p36 found in this tumor, they assign RIZ a potential role in the multi-step tumor forming process of malignant melanoma of the skin.