Schönleben Frank, Qiu Wanglong, Bruckman Karl C, Ciau Nancy T, Li Xiaojun, Lauerman Margaret H, Frucht Harold, Chabot John A, Allendorf John D, Remotti Helen E, Su Gloria H
Department of Otolaryngology/Head and Neck Surgery, Columbia University, College of Physicians and Surgeons, 1130 St. Nicholas Ave, ICRC 10-04, New York, NY 10032, USA.
Cancer Lett. 2007 May 8;249(2):242-8. doi: 10.1016/j.canlet.2006.09.007. Epub 2006 Nov 9.
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.
Raf/MEK/ERK（丝裂原活化蛋白激酶）信号转导是包括生长、增殖和存活在内的多种细胞命运的重要介导因子。BRAF基因被致癌性RAS激活，在对生长因子信号作出反应的细胞中产生协同效应。我们开展这项研究以阐明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癌（IPMC）发生过程中可能发挥的作用。通过直接基因组测序对36例IPMN/IPMC样本和2例黏液性囊腺瘤中的BRAF和KRAS突变进行评估。检测了KRAS的第1外显子以及BRAF的第5、11和15外显子。我们共在BRAF第15外显子中鉴定出17个（47%）位于第1外显子密码子12处的KRAS突变和1个错义突变（2.7%）。这些突变似乎是体细胞突变，因为在相应的正常组织中未检测到相同的改变。我们的数据表明BRAF的致癌特性有助于IPMN/IPMC的肿瘤发生，但频率低于KRAS。
