BACKGROUND: Mutations of KRAS are known to occur in periampullary and ampullary 
adenomas and carcinomas. However, nothing is known about NRAS, HRAS, BRAF, and 
PIK3CA mutations in these tumors. While oncogenic BRAF contributes to the 
tumorigenesis of both pancreatic ductal adenocarcinoma and intraductal papillary 
mucinous neoplasms/carcinomas (IPMN/IPMC), PIK3CA mutations were only detected 
in IPMN/IPMC. This study aimed to elucidate possible roles of BRAF and PIK3CA in 
the development of ampullary and periampullary adenomas and carcinomas.
METHODS: Mutations of BRAF, NRAS, HRAS, KRAS, and PIK3CA were evaluated in seven 
adenomas, seven adenomas with carcinoma in situ, and 21 adenocarcinomas of the 
periampullary duodenal region and the ampulla of Vater. Exons 1 of KRAS; 2 and 3 
of NRAS and HRAS; 5, 11, and 15 of BRAF; and 9 and 20 of PIK3CA were examined by 
direct genomic sequencing.
RESULTS: In total, we identified ten (28.6%) KRAS mutations in exon 1 (nine in 
codon 12 and one in codon 13), two missense mutations of BRAF (6%), one within 
exon 11 (G469A), and one V600E hot spot mutation in exon 15 of BRAF. BRAF 
mutations were present in two of five periampullary tumors. All mutations appear 
to be somatic since the same alterations were not detected in the corresponding 
normal tissues.
CONCLUSION: Our data provide evidence that oncogenic properties of KRAS and BRAF 
but not NRAS, HRAS, and PIK3CA contribute to the tumorigenesis of periampullary 
and ampullary tumors; BRAF mutations occur more frequently in periampullary than 
ampullary neoplasms.