Mutations of PIK3CA in gastric adenocarcinoma.
Mutations of PIK3CA in gastric adenocarcinoma.
复制标题
胃腺癌中PIK3CA的突变。
DOI：
10.1186/1471-2407-5-29
复制
发表时间：
2005-03-23
期刊：
影响因子：
3.8
通讯作者：
Leung, SY
中科院分区：
文献类型：
--
作者：
Li, VSW;Wong, CW;Chan, TL;Chan, ASW;Zhao, W;Chu, KM;So, S;Chen, X;Yuen, ST;Leung, SY
通过突变失活的PTEN肿瘤抑制基因的磷脂酰肌醇3-激酶（PI 3 K）的激活是常见的各种癌症类型，但很少报告在胃癌。最近，已在多种人类癌症（包括12种胃癌中的3种）中鉴定出编码PI 3 K的p110α催化亚基的PIK 3CA突变。这些报告的突变中有80%聚集在涉及螺旋和激酶结构域的2个区域内。对其中一个“热点”突变体的体外研究表明它是一种激活突变。在此基础上，我们对94例胃癌组织进行了PIK 3CA基因突变筛查，其中80%的PIK 3CA基因突变发生在胃癌组织中，并提取了大规模基因表达谱研究的数据，对PIK 3CA基因表达水平进行了检测。使用微阵列的显著性分析（SAM），我们进一步搜索显示与PIK 3CA相关表达的基因。我们在4例病例（4.3%）中发现了PIK 3CA突变，均涉及先前报道的热点。在这4例病例中，3例肿瘤表现出微卫星不稳定性，2例肿瘤同时存在KRAS突变。从微阵列研究中提取的数据显示，与非肿瘤性胃粘膜相比，胃癌中PIK 3CA的表达增加（p < 0.001）。SAM进一步鉴定了2910个基因，其表达水平与PIK 3CA的表达水平正相关。我们的数据表明，胃癌中PI 3 K信号通路的激活可能是通过上调或突变PIK 3CA来实现的，其中后者可能是错配修复缺陷的结果。
Activation of the phosphatidylinositol 3-kinase (PI3K) through mutational inactivation of PTEN tumour suppressor gene is common in diverse cancer types, but rarely reported in gastric cancer. Recently, mutations in PIK3CA, which encodes the p110α catalytic subunit of PI3K, have been identified in various human cancers, including 3 of 12 gastric cancers. Eighty percent of these reported mutations clustered within 2 regions involving the helical and kinase domains. In vitro study on one of the "hot-spot" mutants has demonstrated it as an activating mutation. Based on these data, we initiated PIK3CA mutation screening in 94 human gastric cancers by direct sequencing of the gene regions in which 80% of all the known PIK3CA mutations were found. We also examined PIK3CA expression level by extracting data from the previous large-scale gene expression profiling study. Using Significance Analysis of Microarrays (SAM), we further searched for genes that show correlating expression with PIK3CA. We have identified PIK3CA mutations in 4 cases (4.3%), all involving the previously reported hotspots. Among these 4 cases, 3 tumours demonstrated microsatellite instability and 2 tumours harboured concurrent KRAS mutation. Data extracted from microarray studies showed an increased expression of PIK3CA in gastric cancers when compared with the non-neoplastic gastric mucosae (p < 0.001). SAM further identified 2910 genes whose expression levels were positively associated with that of PIK3CA. Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency.
登录
查看更多内容
影响因子：
64.8
作者：
Rajagopalan, H;Bardelli, A;Velculescu, VE
通讯作者：
Velculescu, VE
DOI：
10.1073/pnas.84.14.5034
发表时间：
1987-07-01
影响因子：
11.1
作者：
STAAL, SP
通讯作者：
STAAL, SP
影响因子：
7.3
作者：
Woenckhaus, J;Steger, K;Stahl, U
通讯作者：
Stahl, U
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
影响因子：
6.4
作者：
Byun, DS;Cho, K;Chi, SG
通讯作者：
Chi, SG