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Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in anaplastic thyroid cancer

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Abstract

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer with a median survival of 4–6 months. Identification of mutations contributing to aberrant activation of signaling cascades in ATC may provide novel opportunities for targeted therapy. Thirty-nine ATC samples were studied by next-generation sequencing (NGS) with an established gene panel. High quality readout was obtained in 30/39 ATC. Twenty-eight ATC harbored a mutation in at least one of the studied genes: TP53 (18/30), NF1 (11/30), ALK (6/30), NRAS (4/30), ATRX (3/30), BRAF (2/30), HRAS (2/30), KRAS (1/30). In 17/30 ATC (54 %) mutations were found in two or more genes. Twenty-one of the identified variants are listed in COSMIC as somatic mutations reported in other cancer entities. In three ATC samples no mutations were detected and none of the ATCs was positive for BRAFV600E. The most frequent mutations were found in TP53 (60 %), followed by NF1 (37 %). ALK mutations were detected in 20 % of ATC and were more frequent than RAS or BRAF mutations. ATRX mutations were identified in 10 % of the ATC samples. These sequencing data from 30 ATC samples demonstrate the accumulation of genetic alterations in ATC because in 90 % of samples mutations were already found in the investigated nine genes alone. Mutations were found with high prevalence in established tumor suppressor and oncogenes in ATC, such as TP53 and H/K/NRAS, but also, although less frequent, in genes that may harbor the potential for targeted treatment in a subset of ATC patients, such as ALK and NF1.

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Funding

This work was supported by the Deutsche Forschungsgemeinschaft DFG (FU356 3-3 to D.F.).

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  1. Department of Endocrinology and Metabolism, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, Essen, 45122, Germany

    Soeren Latteyer, Vera Tiedje, Dagmar Führer & Lars Christian Moeller

  2. Institute of Pathology, University Hospital Cologne, Kerpener Straße 62, Cologne, 50935, Germany

    Katharina König & Lydia Meder

  3. Labor Dr. Quade und Kollegen GmbH, Medizinisches Versorgungszentrum, Aachener Str. 338, Cologne, 50933, Germany

    Katharina König

  4. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, Essen, 45122, Germany

    Saskia Ting & Kurt Werner Schmid

  5. NEO New Oncology AG, Gottfried-Hagen-Str. 20, Cologne, 51105, Germany

    Lukas C. Heukamp

  6. Institute of Hematopathology Hamburg, Fangdieckstraße 75a, Hamburg, 22547, Germany

    Lukas C. Heukamp

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Latteyer, S., Tiedje, V., König, K. et al. Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in anaplastic thyroid cancer. Endocrine 54, 733–741 (2016). https://doi.org/10.1007/s12020-016-1080-9

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