title: A molecular signature for oncogenic BRAF in human colon cancer cells is revealed by microarray analysis.
abstract: Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell lines that also showed an EMT phenotype for HRAS. In this study we report a molecular profile for a BRAF oncogenic mutation BRAFV600E in colon using the Illumina 45,000 gene microarray. Key differentially expressed genes have been identified from the array analysis further verified by qPCR analysis. Ingenuity pathway analysis such as microsatellite instability, kinase signalling, apoptosis, WNT and Integrin signalling is presented. MutBRAF transforms cells through cross talk with developmental pathways Hedgehog and Wnt, as well as by deregulation of colorectal cancer related kinase pathways, like PI3K. Differential gene expression of BRAFV600E in colon as compared to those associated with RAS oncogenes is presented, as well as similarities and differences between oncogenic BRAF signatures in colon as compared to thyroid and melanoma are highlighted. Novel selected genes/pathways are validated in cell lines and clinical samples bearing BRAFV600E and may serve as markers/targets for personalised diagnosis/therapy/resistance of colorectal cancer.
authors.affiliation: Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Vas. Constantinou Ave. 48, 11635, Athens, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Joyce
authors.forename: E
authors.initials: E
authors.lastname: Oikonomou
authors.forename: V
authors.initials: V
authors.lastname: Kosmidou
authors.forename: E
authors.initials: E
authors.lastname: Makrodouli
authors.forename: I
authors.initials: I
authors.lastname: Bantounas
authors.forename: S
authors.initials: S
authors.lastname: Avlonitis
authors.forename: G
authors.initials: G
authors.lastname: Zografos
authors.forename: A
authors.initials: A
authors.lastname: Pintzas
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D046228:Microarray Analysis / Q000379:methods; D009154:Mutation; D009857:Oncogenes; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf