Mutation analysis of 24 known cancer genes in the NCI-60 cell line set.
Mutation analysis of 24 known cancer genes in the NCI-60 cell line set.
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DOI：
10.1158/1535-7163.mct-06-0433
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发表时间：
2006-11
影响因子：
5.7
通讯作者：
Wooster R
中科院分区：
文献类型：
--
作者：
Ikediobi ON;Davies H;Bignell G;Edkins S;Stevens C;O'Meara S;Santarius T;Avis T;Barthorpe S;Brackenbury L;Buck G;Butler A;Clements J;Cole J;Dicks E;Forbes S;Gray K;Halliday K;Harrison R;Hills K;Hinton J;Hunter C;Jenkinson A;Jones D;Kosmidou V;Lugg R;Menzies A;Mironenko T;Parker A;Perry J;Raine K;Richardson D;Shepherd R;Small A;Smith R;Solomon H;Stephens P;Teague J;Tofts C;Varian J;Webb T;West S;Widaa S;Yates A;Reinhold W;Weinstein JN;Stratton MR;Futreal PA;Wooster R
由国家癌症研究所为抗癌药物发现而组装的60种人类癌细胞系（NCI-60）是一种广泛使用的资源。与任何其他细胞系相比，NCI-60在药理学和分子水平上的特征更为广泛。然而，没有系统的基因突变分析的因果关系牵连在肿瘤的报告。本研究报告了NCI-60中24个已知癌基因的序列分析，并评估了24个基因中的4个纯合缺失。在24个基因中的14个（APC、BRAF、CDKN 2、CTNNB 1、HRAS、KRAS、NRAS、SMAD 4、PIK 3CA、PTEN、RB 1、STK 11、TP 53和VHL）中鉴定了137个致癌突变。所有品系在检测的癌症基因中至少有一个突变，大多数品系（73%）有一个以上的突变。鉴定NCI-60中突变的那些癌症基因，结合细胞的药理学和分子特征，将允许对抗癌剂筛选进行更明智的解释，并将增强NCI-60细胞系用于分子靶向筛选的用途。
The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.