PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas.
PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas.
复制标题
胰腺导管内乳头状粘液性肿瘤/癌 (IPMN/C) 中的 PIK3CA、KRAS 和 BRAF 突变。
DOI：
10.1007/s00423-008-0285-7
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Su,GloriaH
中科院分区：
文献类型：
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作者：
Schönleben,Frank;Qiu,Wanglong;Remotti,HelenE;Hohenberger,Werner;Su,GloriaH
背景和目的最近的研究报道了多种人类肿瘤中磷酸肌醇-3激酶催化-α (PIK3CA)基因的高频率体细胞突变。外显子9和20的三个热点突变已被证明可以激活Akt信号通路。Raf/MEK/ERK（丝裂原活化蛋白激酶）信号转导是包括生长、增殖和存活在内的许多细胞命运的重要介质。BRAF基因被致癌RAS激活，导致细胞响应生长因子信号的协同效应。本研究评估了PIK3CA、KRAS和BRAF在胰腺导管内乳头状黏液性肿瘤/癌（IPMN/IPMNC）中的突变状态。材料和方法对36例IPMN/IPMC和2例粘液囊腺瘤标本进行直接基因组DNA测序，分析pik3ca基因1、4、5、6、7、9、12、18、20号子，kras基因1号外显子，brf基因5、11、15号外显子。结果在36例IPMN/IPMC标本中鉴定出4个PIK3CA体细胞错义突变（11%）。四种突变中的一种H1047R，此前曾被报道为热点突变。此外，我们发现BRAF外显子1有17个（47%）KRAS突变，外显子15有1个错义突变（2.7%）。结论pik3突变在胰腺癌中首次报道，它似乎是IPMN/IPMC中第一个突变的癌基因，而不是在传统的胰腺导管腺癌中。我们的数据提供了pik3caandbrf促进IPMN/IPMC肿瘤发生的证据，但在较低的频率上。
Background and aimsRecent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-α (PIK3CA) gene in various human tumors. Three hot-spot mutations in the exons 9 and 20 have been proven to activate the Akt signalling pathway. The Raf/MEK/ERK (mitogen-activated protein kinase) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Here we evaluate the mutational status of PIK3CA, KRAS, and BRAF in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMNC) of the pancreas.Materials and methodsExons 1, 4, 5, 6, 7, 9, 12, 18, and 20 ofPIK3CA, exons 1 ofKRAS, and exons 5, 11, and 15 ofBRAFwere analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing.ResultsWe identified four somatic missense mutations of PIK3CA within the 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported to be a hot-spot mutation. Furthermore, we found 17 (47%) KRAS mutations in exon 1 and one missense mutation (2.7%) in exon 15 of BRAF.ConclusionThis data is the first report ofPIK3CAmutation in pancreatic cancer and it appears to be the first oncogene to be mutated in IPMN/IPMC but not in conventional ductal adenocarcinoma of the pancreas. Our data provide evidence thatPIK3CAandBRAFcontribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency thanKRAS.