PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas
PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas
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DOI：
10.1158/1078-0432.ccr-06-0292
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发表时间：
2006-06-15
影响因子：
11.5
通讯作者：
Su, Gloria H.
中科院分区：
文献类型：
--
作者：
Schoenleben, Frank;Qiu, Wanglong;Su, Gloria H.
目的：最近的研究报告了各种人类实体瘤中磷酸肌醇-3-激酶催化-α（PIK 3CA）基因的高频率体细胞突变。超过75%的这些体细胞突变聚集在螺旋（外显子9）和激酶结构域（外显子20）。三个热点突变E542 K、E545 K和H1047 R已被证明提高PIK 3CA的脂质激酶活性并激活Akt信号通路。（IPMN/IPMC）之前没有被评估过。为了评估PIK 3CA在IPMN和IPMC肿瘤发生中的可能作用，通过直接基因组DNA测序分析了36个IPMN/IPMC和两个粘液性囊腺瘤标本中的外显子1、4、5、6、7、9、12、18和20。我们从36例IPMN/IPMC标本（11%）中发现了9个筛选的PIK 3CA外显子中的4个错义突变。这四个突变之一，H1047 R，以前曾被报道为热点突变。其余3个突变T3241、W551 G和S1015 F均为新的体细胞突变。结论：本研究首次报道胰腺癌中PIK 3CA突变。我们的数据提供了PIK 3CA的致癌特性有助于IPMN/ IPMC的肿瘤发生的证据。
Purpose: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in various human solid tumors. More than 75% of those somatic mutations are clustered in the helical (exon 9) and kinase domains (exon 20). The three hot-spot mutations, E542K, E545K, and H1047R, have been proven to elevate the lipid kinase activity of PIK3CA and activate the Akt signaling pathway, The mutational status of PIK3CA in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) has not been evaluated previously.Experimental Design: To evaluate a possible role for PIK3CA in the tumorigenesis of IPMN and IPMC, exons 1, 4, 5, 6, 7, 9,12,18, and 20 were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing.Results: We identified four missense mutations in the nine screened exons of PIK3CA from 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported as a hot-spot mutation. The remaining three mutations, T3241, W551G, and S1015F, were novel and somatic.Conclusion: This is the first report of PIK3CA mutation in pancreatic cancer. Our data provide evidence that the oncogenic properties of PIK3CA contribute to the tumorigenesis of IPMN/ IPMC.