IRS2 is a candidate driver oncogene on 13q34 in colorectal cancer.
IRS2 is a candidate driver oncogene on 13q34 in colorectal cancer.
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DOI：
10.1111/iep.12021
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发表时间：
2013-06
影响因子：
3
通讯作者：
Dear PH
中科院分区：
文献类型：
--
作者：
Day E;Poulogiannis G;McCaughan F;Mulholland S;Arends MJ;Ibrahim AE;Dear PH
拷贝数的改变经常在结直肠癌（CRC）中发现，并且复发性的增加或减少可能分别对应于携带促进或阻碍致癌作用的基因的区域。染色体13 q的增加在CRC中很常见，但由于增加区域通常很大，因此迄今为止证明驱动基因的识别很困难。我们使用阵列比较基因组杂交分析了124个原发性CRC，表明13 q34是35% CRC的增益区域，4%的病灶增益和1.6%的病例扩增。为了减少要考虑的潜在驱动基因的数量，有必要细化该系列中观察到的最小拷贝数变化的边界，从而定义最小拷贝区（MCR）。这是使用分子拷贝数计数进行的，将IRS 2鉴定为唯一完整的基因，因此可能是改良MCR中的驱动致癌基因。对现有结直肠肿瘤数据集的分析证实IRS 2基因获得是一种常见事件。此外，IRS 2蛋白和mRNA在结直肠肿瘤中的表达与从正常到腺瘤到癌的进展呈正相关。在功能性体外实验中，我们证明IRS 2的表达失调激活致癌PI 3激酶通路并增加细胞粘附，这两个特征都是侵袭性CRC细胞的特征。总之，这些数据将IRS 2鉴定为常见的13 q34增益/扩增区域中可能的驱动致癌基因，并表明IRS 2过表达可能提供CRC中PI 3激酶途径活化的额外机制。
Copy number alterations are frequently found in colorectal cancer (CRC), and recurrent gains or losses are likely to correspond to regions harbouring genes that promote or impede carcinogenesis respectively. Gain of chromosome 13q is common in CRC but, because the region of gain is frequently large, identification of the driver gene(s) has hitherto proved difficult. We used array comparative genomic hybridization to analyse 124 primary CRCs, demonstrating that 13q34 is a region of gain in 35% of CRCs, with focal gains in 4% and amplification in a further 1.6% of cases. To reduce the number of potential driver genes to consider, it was necessary to refine the boundaries of the narrowest copy number changes seen in this series and hence define the minimal copy region (MCR). This was performed using molecular copy-number counting, identifying IRS2 as the only complete gene, and therefore the likely driver oncogene, within the refined MCR. Analysis of available colorectal neoplasia data sets confirmed IRS2 gene gain as a common event. Furthermore, IRS2 protein and mRNA expression in colorectal neoplasia was assessed and was positively correlated with progression from normal through adenoma to carcinoma. In functional in vitro experiments, we demonstrate that deregulated expression of IRS2 activates the oncogenic PI3 kinase pathway and increases cell adhesion, both characteristics of invasive CRC cells. Together, these data identify IRS2 as a likely driver oncogene in the prevalent 13q34 region of gain/amplification and suggest that IRS2 over-expression may provide an additional mechanism of PI3 kinase pathway activation in CRC.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1158/1940-6207.capr-09-0199
发表时间：
2010-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
McCampbell AS;Harris HA;Crabtree JS;Winneker RC;Walker CL;Broaddus RR
通讯作者：
Broaddus RR
影响因子：
8
作者：
Jackson, JG;Zhang, XH;Yee, D
通讯作者：
Yee, D
DOI：
10.1083/jcb.200408161
发表时间：
2004-11-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Manning BD
通讯作者：
Manning BD
DOI：
10.1186/1478-811x-7-14
发表时间：
2009-06-17
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Mardilovich K;Pankratz SL;Shaw LM
通讯作者：
Shaw LM