Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma

Microdissection
DOI: 10.1136/gut.52.5.706 Publication Date: 2003-04-11T21:58:41Z
ABSTRACT
The Raf/MEK/ERK (mitogen activated protein kinase-MAPK) signal transduction cascade is an important mediator of a number cellular fates, including growth, proliferation, and survival. BRAF gene, one the human isoforms RAF, by oncogenic Ras, leading to cooperative effects in cells responding growth factor signals.The aim this study was elucidate possible function liver tumours.Mutations KRAS were evaluated 25 hepatocellular carcinomas (HCC) 69 cholangiocarcinomas (CC) direct DNA sequencing analyses after microdissection. presence active intermediates MAPK pathway assessed immunohistochemically. results obtained correlated with histopathological variables patient survival.Activating missense mutations identified 15/69 CC (22%) case tumour surrounding liver. found 31 (45%) examined two cases non-neoplastic tissue. In HCC, neither nor detected. All had intact gene. We failed observe correlation between or factors prognosis patients.Our data indicate that gene are relatively common event but not HCC. Disruption (MAPK) kinase pathway, either RAS mutation, detected approximately 62% all therefore most frequent defects cholangiocellular carcinogenesis.
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