KRAS and PIK3CA but not BRAF genes are frequently mutated in Chinese cholangiocarcinoma patients
KRAS and PIK3CA but not BRAF genes are frequently mutated in Chinese cholangiocarcinoma patients
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DOI：
10.1016/j.biopha.2010.06.009
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发表时间：
2011-02-01
影响因子：
7.5
通讯作者：
Liao, Wang Jun
中科院分区：
文献类型：
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作者：
Xu, Rui Feng;Sun, Ji Ping;Liao, Wang Jun
胆管癌是一种罕见但致命的恶性肿瘤，起源于胆道上皮。由于早期诊断困难和缺乏有效的治疗方法，其预后很差。因此，迫切需要开发新的和有效的治疗CCA，这在很大程度上取决于对疾病的机制的理解。以前的研究表明，KRAS，BRAF和PIK3CA基因的体细胞突变经常在几种类型的人类癌症中发现，包括结肠癌，乳腺癌和肺癌以及CCA。然而，在中国人群中，这些致癌突变的频率和参与CCA还没有调查。在本研究中，我们评估了34例中国CCA患者的KRAS、BRAF和PIK3CA基因的热点突变。测序分析显示13例（38.2%）和11例（32.4%）患者携带KRAS和PIK3CA突变，其中2例（5.9%）患者同时携带KRAS和PIK3CA突变。令人惊讶的是，在所有34个CCA样品中均未检测到BRAF突变。我们的研究结果表明，KRAS和PIK3CA而不是BRAF癌基因的体细胞突变与中国人群中CCA的发展密切相关，并为未来治疗该疾病提供了新的潜在靶点。(C)2010年Elsevier Masson SAS。All rights reserved.
Cholangiocarcinoma (CCA) is a rare but lethal malignancy arising from the biliary tract epithelium. It has a poor prognosis largely due to the difficulties of early diagnosis and the lack of effective therapies. It is thus imperative to develop new and effective treatments for CCA, which depends heavily on the mechanistic understanding of the disease. Previous studies have suggested that somatic mutations in KRAS, BRAF, and PIK3CA genes are frequently found in several types of human cancers including colon, breast, and lung carcinomas as well as CCA. Yet, the frequency and the involvement of these oncogenic mutations in CCA in Chinese population have not been investigated. In this study, we evaluated the hotspot mutations of KRAS, BRAF, and PIK3CA genes in 34 Chinese CCA patients. Sequencing analysis revealed 13 (38.2%) and 11 (32.4%) patients bearing KRAS and PIK3CA mutations, in which two (5.9%) of them harbored both KRAS and PIK3CA mutations. Surprisingly, no BRAF mutation was detected in all 34 CCA samples. Our findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of CCA in Chinese population and provide new potential targets for future therapeutic treatments of the disease. (C) 2010 Elsevier Masson SAS. All rights reserved.