title: Search for new genetic biomarkers in poorly differentiated and anaplastic thyroid carcinomas using next generation sequencing.
abstract: BACKGROUND
  Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are very rare tumors with extremely aggressive behavior. Their comprehensive genetic background is still unclear. Some of the main genetic changes of differentiated thyroid carcinomas, such as mutations in BRAF and RAS genes, as well as changes in CTNNB1, PIK3CA, TP53, AXIN1, PTEN or APC genes leading to the dedifferentiation of the tumors, are described.
  
  
  METHODS
  DNAs from fresh frozen thyroid tissues of 3 PDTCs and 5 ATCs were extracted. The next-generation sequencing (NGS) approach was used to target 94 genes involved in cancer. The samples were prepared using a TruSight Cancer panel and sequenced with a MiSeq sequencer. Analysis of variants was performed by the MiSeq Reporter and NextGENe software and stringent criteria for prioritization of the variants were used in the Illumina VariantStudio software.
  
  
  RESULTS
  Using NGS, we identified 26 genetic changes in 18 genes, novel variants included.
  
  
  CONCLUSIONS
  NGS is a useful tool for searching for new variants and genes involved in PDTC and ATC. It seems that each of these rare tumor types has its own specific genetic background. These data could be helpful for recognizing new genetic markers and targets for future personalized therapy.
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic vsykorova@endo.cz.
authors: Vlasta
authors: V
authors: Sykorova
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic.
authors: Sarka
authors: S
authors: Dvorakova
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic.
authors: Josef
authors: J
authors: Vcelak
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic.
authors: Eliska
authors: E
authors: Vaclavikova
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic.
authors: Tereza
authors: T
authors: Halkova
authors: Departments of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors: Daniela
authors: D
authors: Kodetova
authors: Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors: Petr
authors: P
authors: Lastuvka
authors: Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors: Jan
authors: J
authors: Betka
authors: Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors: Petr
authors: P
authors: Vlcek
authors: Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague 2, Czech Republic.
authors: Martin
authors: M
authors: Reboun
authors: Department of ENT, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.
authors: Rami
authors: R
authors: Katra
authors: Department of Molecular Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic.
authors: Bela
authors: B
authors: Bendlova
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000302:isolation & purification; D002454:Cell Differentiation / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Anaplastic thyroid carcinoma; genetics; next-generation sequencing; poorly differentiated thyroid carcinoma