Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines
Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines
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DOI：
10.1002/gcc.20260
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
Lam, WL
中科院分区：
文献类型：
--
作者：
Coe, BR;Lee, EHL;Lam, WL
小细胞肺癌(SCLC)是一种侵袭性很强的肺癌，占每年肺癌病例的20%。对小细胞肺癌前体细胞类型的缺乏阻碍了对正常基因表达谱的定义，并阻碍了对基因表达变化的识别，而传统基因组筛选的低分辨率，如比较基因组杂交(CGH)和杂合性丢失分析，限制了我们精细定位遗传变化的能力。最近出现的全基因组拼接路径阵列CGH使得能够以传统方法100倍的分辨率来分析片段DNA拷贝数的增减。在这里，我们报告了14个小细胞肺癌细胞系和6个配对的正常B淋巴细胞系的分析。我们在14个小细胞肺癌细胞系中有13个检测到7p22.3拷贝数增加，而在6个匹配的正常细胞系中检测到0个。在14个细胞系中的4个中，这种增加表现为以MADILI(酵母基因MADI的人类同源物)为中心的350kbp基因特异性拷贝数增加。荧光原位杂交验证了阵列CGH的发现。有趣的是，MADILI被认为具有抑制肿瘤的功能。我们的数据提示该基因的作用更为复杂，因为MAD I L I是小细胞肺癌细胞系中最常见的拷贝数增加。(C)2005年Wiley-Liss，Inc.
Small-cell lung cancer (SCLC) is a highly aggressive lung neoplasm, which accounts for 20% of yearly lung cancer cases. The lack of knowledge of the progenitor cell type for SCLC precludes the definition of a normal gene expression profile and has hampered the identification of gene expression changes, while the low resolution of conventional genomic screens such as comparative genomic hybridization (CGH) and loss of heterozygosity analysis limit our ability to fine-map genetic alterations. The recent advent of whole genome tiling path array CGH enables profiling of segmental DNA copy number gains and losses at a resolution 100 times that of conventional methods. Here we report the analysis of 14 SCLC cell lines and six matched normal B-lymphocyte lines. We detected 7p22.3 copy number gain in 13 of the 14 SCLC lines and 0 of the 6 matched normal lines. In 4 of the 14 cell lines, this gain is present as a 350 kbp gene specific copy number gain centered at MADILI (the human homologue of the yeast gene MADI). Fluorescence in situ hybridization validated the array CGH finding. Intriguingly, MADILI has been implicated to have tumor-suppressing functions. Our data suggest a more complex role for this gene, as MAD I L I is the most frequent copy number gain in SCLC cell lines. (c) 2005 Wiley-Liss, Inc.