title: Mutations leading to constitutive active gp130/JAK1/STAT3 pathway.
abstract: Constitutive activation of STAT (Signal Transducer and Activator of Transcription) transcription factors is a common feature identified in numerous tumors. Inflammatory hepatocellular adenomas (IHCA) are benign liver tumors characterized by an inflammatory phenotype and an overexpression of STAT3 target genes. Recurrent somatic mutations in major actors belonging to the IL6/JAK/STAT3 pathway have been identified in these tumors. (1) 60% of IHCA show IL-6 signal transducer (IL6ST; gp130) mutations; (2) 10% harbor mutations of the Fyn-related kinase FRK; (3) 5% harbor mutations in STAT3; (4) 5% harbor somatic mutations in the GNAS complex locus; and (5) 1% of IHCA harbor mutations in the Janus kinase 1 (JAK1). All these IHCA-associated mutations promote the constitutive activation of STAT3. In this review, we discuss the role of these mutated genes in IHCA and other tumors.
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des Tumeurs solides, Equipe Labellisée Ligue Contre le Cancer, Paris F-75010, France; Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France; Université Paris Diderot, F-75013 Paris, France; Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou, F-75015 Paris, France.
authors.forename: Camilla
authors.initials: C
authors.lastname: Pilati
authors.affiliation: Inserm, UMR-1162, Génomique fonctionnelle des Tumeurs solides, Equipe Labellisée Ligue Contre le Cancer, Paris F-75010, France; Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France; Université Paris Diderot, F-75013 Paris, France; Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou, F-75015 Paris, France. Electronic address: jessica.zucman-rossi@inserm.fr.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
mesh_terms: D000818:Animals; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics / Q000276:immunology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: C494199:IL6ST protein, human; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human; C507904:JAK1 protein, human; D053613:Janus Kinase 1
keywords: FRK; GNAS; Inflammatory hepatocellular adenomas; JAK1; STAT3; gp130