1. ¹Department of Otolaryngology—Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
2. ²Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
3. ³Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
4. ⁴Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
5. ⁵Department of Medicine, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA

Correspondence: Dr A Maitra, MBBS, Department of Pathology, Ross 632, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. E-mail: amaitra1@jhmi.edu

Received 8 January 2004; Revised 4 March 2004; Accepted 5 March 2004; Published online 4 June 2004.

Abstract

Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation—V599E—accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector^® assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study.