BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas

Abstract 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...

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Bibliographic Details
Published in:Cancer letters 2007-05, Vol.249 (2), p.242-248
Main Authors: Schönleben, Frank, Qiu, Wanglong, Bruckman, Karl C, Ciau, Nancy T, Li, Xiaojun, Lauerman, Margaret H, Frucht, Harold, Chabot, John A, Allendorf, John D, Remotti, Helen E, Su, Gloria H
Format: Article
Language:English
Subjects:
Adenocarcinoma, Mucinous - genetics
Adenocarcinoma, Papillary - genetics
Adult
Age
Aged
Aged, 80 and over
BRAF
Cancer
Carcinoma, Pancreatic Ductal - genetics
Deoxyribonucleic acid
DNA
DNA methylation
Female
Genes
Genes, ras - genetics
Genetic testing
Health Insurance Portability & Accountability Act 1996-US
Hematology, Oncology and Palliative Medicine
Humans
Intraductal papillary mucinous neoplasm
Kinases
KRAS
Male
Middle Aged
Mutation
Pancreas
Pancreatic Neoplasms - genetics
Proteins
Proto-Oncogene Proteins B-raf - genetics
Tumors
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Summary:Abstract 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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2006.09.007