title: New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma.
abstract: Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignant neoplasia. Oncogene activation occurs in more than 70% of the cases. Indeed, about 40% of PTCs harbor mutations in BRAF gene, whereas RET rearrangements (RET/PTC oncogenes) are present in about 20% of cases. Finally, RAS mutations and TRK rearrangements account for about 5% each of these malignancies. We used RNA-Sequencing to identify fusion transcripts and mutations in cancer driver genes in a cohort of 18 PTC patients. Furthermore, we used targeted DNA sequencing to validate identified mutations. We extended the screening to 50 PTC patients and 30 healthy individuals. Using this approach we identified new missense mutations in CBL, NOTCH1, PIK3R4 and SMARCA4 genes. We found somatic mutations in DICER1, MET and VHL genes, previously found mutated in other tumors, but not described in PTC. We identified a new chimeric transcript generated by the fusion of WNK1 and B4GALNT3 genes, correlated with B4GALNT3 overexpression. Our data confirmed PTC genetic heterogeneity, revealing that gene expression correlates more with the mutation pattern than with tumor staging. Overall, this study provides new data about mutational landscape of this neoplasia, suggesting potential pharmacological adjuvant therapies against Notch signaling and chromatin remodeling enzymes.
authors: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, Naples, Italy.
authors: Valerio
authors: V
authors: Costa
authors: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, Naples, Italy.
authors: Roberta
authors: R
authors: Esposito
authors: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, Naples, Italy.
authors: Carmela
authors: C
authors: Ziviello
authors: Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Naples, Italy.
authors: Romina
authors: R
authors: Sepe
authors: Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Naples, Italy.
authors: Larissa Valdemarin
authors: LV
authors: Bim
authors: Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Naples, Italy.
authors: Nunzio Antonio
authors: NA
authors: Cacciola
authors: Department of Pathology, Lyon Sud Hospital Center, Hospices Civils de Lyon, Pierre-Bénite, Lyon, France.
authors: Myriam
authors: M
authors: Decaussin-Petrucci
authors: Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Naples, Italy.
authors: Pierlorenzo
authors: P
authors: Pallante
authors: Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS), Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Naples, Italy.|Instituto Nacional de Câncer - INCA, Praça da Cruz Vermelha, Rio de Janeiro, RJ, Brazil.
authors: Alfredo
authors: A
authors: Fusco
authors: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, Naples, Italy.|Department of Science and Technology, University "Parthenope" of Naples, Naples, Italy.
authors: Alfredo
authors: A
authors: Ciccodicola
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics; D004252:DNA Mutational Analysis; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D020125:Mutation, Missense; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D015203:Reproducibility of Results; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D058571:Vacuolar Sorting Protein VPS15 / Q000235:genetics; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; C497761:NOTCH1 protein, human; D009687:Nuclear Proteins; D051881:Receptor, Notch1; D014157:Transcription Factors; D050721:Proto-Oncogene Proteins c-cbl; C480161:B4GALNT3 protein, human; D017350:N-Acetylgalactosaminyltransferases; C546851:PIK3R4 protein, human; D017346:Protein Serine-Threonine Kinases; D058571:Vacuolar Sorting Protein VPS15; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; C084108:SMARCA4 protein, human; D004265:DNA Helicases; C067419:CBL protein, human
keywords: RNA-sequencing; gene fusions; mutations; papillary carcinomas; thyroid