BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.
BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.
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DOI：
10.1016/j.canlet.2006.09.007
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发表时间：
2007-05
期刊：
影响因子：
9.7
通讯作者：
F. Schönleben;Wanglong Qiu;Karl C. Bruckman;N. Ciau;Xiaojun Li;Margaret H. Lauerman;H. Frucht;J. Chabot;J. Allendorf;H. Remotti;G. Su
中科院分区：
文献类型：
--
作者：
F. Schönleben;Wanglong Qiu;Karl C. Bruckman;N. Ciau;Xiaojun Li;Margaret H. Lauerman;H. Frucht;J. Chabot;J. Allendorf;H. Remotti;G. Su
Raf/MEK/ERK（MAPK）信号转导是许多细胞命运（包括生长、增殖和存活）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。我们的研究旨在阐明BRAF在胰腺导管内乳头状黏液性肿瘤（IPMN）和导管内乳头状黏液性癌（IPMC）发生发展中的可能作用。通过直接基因组测序在36个IPMN/IPMC样本和两个粘液性囊腺瘤中评估BRAF和KRAS突变。检查KRAS的外显子1和BRAF的外显子5、11和15。共发现17例（47%）KRAS突变位于BRAF的第1外显子、第12密码子和1例（2.7%）错义突变位于BRAF的第15外显子。突变似乎是体细胞的，因为在相应的正常组织中没有检测到相同的改变。我们的数据提供的证据表明，BRAF的致癌特性有助于IPMN/IPMC的肿瘤发生，但在较低的频率比KRAS。
The Raf/MEK/ERK (MAPK) 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. Our study was performed to elucidate a possible role of BRAF in the development of IPMN (Intraductal Papillary Mucinous Neoplasm) and IPMC (Intraductal Papillary Mucinous Carcinoma) of the pancreas. Mutations of BRAF and KRAS were evaluated in 36 IPMN/IPMC samples and two mucinous cystadenomas by direct genomic sequencing. Exons 1 for KRAS, and 5, 11, and 15 for BRAF were examined. Totally we identified 17 (47%) KRAS mutations in exon 1, codon 12 and one missense mutation (2.7%) within exon 15 of BRAF. The mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. Our data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.