甲状腺乳头状癌中的BRAF突变

BRAF mutations in papillary carcinomas of the thyroid.

作者信息

Fukushima Toshihiko, Suzuki Shinichi, Mashiko Miyuki, Ohtake Tohru, Endo Yoshiyuki, Takebayashi Yuji, Sekikawa Koji, Hagiwara Koichi, Takenoshita Seiichi

机构信息

Department of Surgery, Fukushima Medical University, 1-Hikarigaoka, Fukushima 960-1295, Japan.

出版信息

Oncogene. 2003 Sep 25;22(41):6455-7. doi: 10.1038/sj.onc.1206739.

DOI:10.1038/sj.onc.1206739

PMID:14508525

Abstract

BRAF is a serine/threonine kinase that receives a mitogenic signal from RAS and transmits it to the MAP kinase pathway. Recent studies have reported that mutations of the BRAF gene were detected with varying frequencies in several cancers, notably more than 60% in melanoma. We analysed mutations of BRAF and RAS genes in 100 cases of thyroid carcinoma to investigate genetic aberrations in the RAS/RAF/MEK/MAP kinase pathway. BRAF mutations were detected exclusively in papillary carcinomas (40 in 76 cases: 53%), and were exclusively V599E, a mutation frequently observed in other carcinomas. NRAS mutation was observed in six cases (6%), all in histological types other than papillary carcinoma, and was exclusively Q61R. No mutations were found in KRAS or HRAS. Our results suggest that BRAF mutations may play a critical role in the carcinogenesis of papillary carcinoma of the thyroid.

摘要

BRAF是一种丝氨酸/苏氨酸激酶，它接收来自RAS的促有丝分裂信号并将其传递至丝裂原活化蛋白激酶（MAP激酶）信号通路。最近的研究报告称，在几种癌症中检测到BRAF基因的突变频率各不相同，在黑色素瘤中尤为明显，超过60%。我们分析了100例甲状腺癌中BRAF和RAS基因的突变情况，以研究RAS/RAF/MEK/MAP激酶信号通路中的基因畸变。BRAF突变仅在乳头状癌中检测到（76例中有40例：53%），且均为V599E，这是在其他癌症中经常观察到的一种突变。NRAS突变在6例（6%）中观察到，均在乳头状癌以外的组织学类型中，且均为Q61R。在KRAS或HRAS中未发现突变。我们的结果表明，BRAF突变可能在甲状腺乳头状癌的致癌过程中起关键作用。