Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at 21q11-21 in human lung cancer
Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at 21q11-21 in human lung cancer
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DOI：
10.1002/gcc.20582
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发表时间：
2008-09-01
影响因子：
3.7
通讯作者：
Takahashi, Takashi
中科院分区：
文献类型：
--
作者：
Yamada, Hideki;Yanagisawa, Kiyoshi;Takahashi, Takashi
肺癌中21 q21的杂合性丢失（洛）的频繁出现提示在该基因组区域存在假定的肿瘤抑制基因。此外，该区域纯合缺失的鉴定进一步支持了其可能参与发病机制。在本研究中，广泛筛选的肺癌细胞系的大面板导致在大细胞肺癌细胞系Calu-6中的21q21.1的纯合性缺失的鉴定。随后的详细表征使我们能够缩小纯合缺失在21q21.1至3.4 Mbp的最短重叠区域的范围。与现有的信息显示的重叠和洛在肺癌中的最短的区域的关系，重叠的1.8-Mbp的区域被认为是一个基因组区域，可能窝藏推定的肿瘤抑制基因的主要候选人。我们发现两个编码基因SAMSNI和USP 2S以及三个miRNA基因miR-99 a、let-7 c和miR-12 Sb-2频繁下调，这些基因位于人类肺癌中常见的缺失区域。此外，初步尝试调查他们的潜在变化和功能参与肺癌的发展。(C)2008 Wiley-Liss，Inc.
The frequent presence of loss of heterozygosity (LOH) at 21q21 in lung cancer suggests the existence of putative tumor suppressor genes in this genomic region. Furthermore, the identification of a homozygous deletion in this region has lent further support for its potential involvement in pathogenesis. In the present study, extensive screening of a large panel of lung cancer cell lines resulted in the identification of a homozygous deletion at 21q21.1 in the large cell lung carcinoma cell line Calu-6. Subsequent detailed characterization allowed us to narrow down the extent of the shortest region of overlap of homozygous deletions at 21q21.1 to 3.4 Mbp. Together with existing information showing a relationship with the shortest region of overlap and LOH in lung cancer, the overlapping 1.8-Mbp region was suggested to be a prime candidate for a genomic region that may harbor putative tumor suppressor genes. We found frequent downregulation of two coding genes, SAMSNI and USP2S, as well as of three miRNA genes, miR-99a, let-7c, and miR-12Sb-2, which reside in the commonly deleted region in human lung cancer. In addition, initial attempts were made to investigate their potential alterations and functional involvements in the development of lung cancer. (C) 2008 Wiley-Liss, Inc.