Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer
Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer
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DOI：
10.1038/sj.onc.1207857
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发表时间：
2004-08-26
期刊：
影响因子：
8
通讯作者：
Wiest, JS
中科院分区：
文献类型：
--
作者：
Shan, ZH;Parker, T;Wiest, JS
杂合性丢失（洛）研究表明，染色体9 p的遗传改变发生在许多肿瘤类型中，提示在染色体9 p上存在肿瘤抑制基因（TSGs），在肿瘤发生中起关键作用。我们先前在原发性肺肿瘤中的洛缺失分析使我们提出染色体9 p含有在肺肿瘤发生中重要的其它TSGs。在这项研究中，30个非小细胞肺癌和12个小细胞肺癌细胞系筛选与55个标记，以确定新的区域的纯合性缺失（HD）的染色体9 p。检测到三个新的非连续同源性缺失区域，大小从840 kb到7.4 Mb不等。在D9 S126处的缺失中鉴定的一个基因，TUSC 1（肿瘤抑制候选物1），是无内含子基因。多重聚合酶链反应和Southern杂交证实了TUSC 1的HD。TUSC 1的北方印迹分析证明了两个大约2和1.5 kb的转录本，它们可能是由替代的多聚腺苷酸化信号产生的。这两种转录本在几种人体组织中表达，并且共享编码209个氨基酸的肽的开放阅读框。通过逆转录酶（RT）-PCR分析细胞系cDNA表明，在有或没有HD的细胞系中TUSC 1下调，表明TUSC 1可能在肺肿瘤发生中发挥作用。
Loss of heterozygosity (LOH) studies indicate that genetic alterations of chromosome 9p occur in numerous tumor types, suggesting the presence of tumor suppressor genes (TSGs) on chromosome 9p critical in carcinogenesis. Our previous LOH analyses in primary lung tumors led us to propose that chromosome 9p harbors other TSGs important in lung tumorigenesis. In this study, 30 non-small-cell lung cancer and 12 small-cell lung cancer cell lines were screened with 55 markers to identify new regions of homozygous deletion (HD) on chromosome 9p. Three novel noncontiguous homozygously deleted regions were detected and ranged in size from 840 kb to 7.4 Mb. One gene identified in the deletion at D9S126, TUSC1 ( tumor suppressor candidate 1), is an intronless gene. Multiplex polymerase chain reaction and Southern blot confirmed the HD of TUSC1. Northern blot analysis of TUSC1 demonstrated two transcripts of approximately 2 and 1.5 kb that are likely generated by alternative polyadenylation signals. Both transcripts are expressed in several human tissues and share an open-reading frame encoding a peptide of 209 amino acids. Analysing cell line cDNAs by reverse transcriptase (RT)-PCR demonstrated downregulation of TUSC1 in cell lines with or without HDs, suggesting that TUSC1 may play a role in lung tumorigenesis.