BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.
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.
Schönleben
Frank
F
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.
Qiu
Wanglong
W
Bruckman
Karl C
KC
Ciau
Nancy T
NT
Li
Xiaojun
X
Lauerman
Margaret H
MH
Frucht
Harold
H
Chabot
John A
JA
Allendorf
John D
JD
Remotti
Helen E
HE
Su
Gloria H
GH
D002288:Adenocarcinoma, Mucinous / Q000235:genetics*; D000231:Adenocarcinoma, Papillary / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf