title: No evidence of ARAF, CRAF and MET mutations in BRAFT1799A negative human papillary thyroid carcinoma.
abstract: The MAPK signaling pathway plays a crucial role in tumorgenesis and cell proliferation in human papillary thyroid carcinoma (PTC). Ret/PTC rearrangements, RAS and BRAF mutations, the main non-overlapping genetic alterations all leading to MAPK cascade activation, are cumulatively identified in 60-80% of PTCs. In approximately one-fourth of the cases, oncogenic background potentially contributing to MAPK activation in PTC might be different. We therefore attempted to evaluate the mutational status of genes encoding other members of RAF family known to act upstream of MAPKs, ARAF and CRAF (RAF-1). In addition we also analyzed the MET gene that encodes hepatocyte growth factor/scatter factor receptor overexpressed in most of PTCs and a MAPK cascade contributor. In 129 Japanese patients with PTC, BRAF(T1799A) was detected in 65 cases (50.4%), and the remaining 64 tumor specimens were subjected to mutation analysis of kinase domains of ARAF, CRAF and MET genes, and hotspots of K- and N-RAS genes. No ARAF, CRAF, MET, K- and N-RAS mutations were revealed. Based on these observations, we concluded that despite the fact that ARAF, CRAF and MET are actively expressed, alterations of these genes are rare in PTC and unlikely to play a perceptible role in the molecular pathogenesis of this type of human malignancy.
authors.affiliation: Department of Molecular Medicine, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagaski, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumagai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Namba
authors.forename: Shu
authors.initials: S
authors.lastname: Takakura
authors.forename: Eiko
authors.initials: E
authors.lastname: Inamasu
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D015870:Gene Expression; D006801:Humans; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D048491:Proto-Oncogene Proteins A-raf / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics* / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C482119:BRAF protein, human; D048491:Proto-Oncogene Proteins A-raf; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf