Oncotarget

Research Papers:

NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma

Vera Tiedje _, Saskia Ting, Thomas Herold, Sarah Synoracki, Soeren Latteyer, Lars C. Moeller, Denise Zwanziger, Martin Stuschke, Dagmar Fuehrer and Kurt Werner Schmid

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:42613-42620. https://doi.org/10.18632/oncotarget.17300

Metrics: PDF 2209 views  |   HTML 1765 views  |   ?  


Abstract

Vera Tiedje1,*, Saskia Ting2,*, Thomas Herold2,3, Sarah Synoracki2, Soeren Latteyer1, Lars C. Moeller1, Denise Zwanziger1, Martin Stuschke4, Dagmar Fuehrer1 and Kurt Werner Schmid2

1Department of Endocrinology and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Duisburg-Essen, Germany

2Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Duisburg-Essen, Germany

3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

4Department of Radiotherapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Duisburg-Essen, Germany

*These authors contributed equally to this work

Correspondence to:

Vera Tiedje, email: vera.tiedje@uk-essen.de

Keywords: next generation sequencing, anaplastic thyroid carcinoma, targeted therapy

Received: November 23, 2016     Accepted: April 11, 2017     Published: April 20, 2017

ABSTRACT

Context: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting “oncogene addiction” of ATC are increasingly explored and first promising results have been reported in single case studies.

Objective: To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC.

Results: In 118 ATC (57 male/ 61 female) a total of 165 mutations were found. Genes involved in the MAPK/ERK and PI3K pathway (BRAF 11.0%, HRAS 4.2%, KRAS 7.6%, NRAS 7.6%, PI3KCA 11.8%) were altered in 33%. Targetable receptor tyrosine kinases were mutated in 11%. The most frequently altered genes were TERT in 86/118 (73%) and p53 in 65/118 (55%) cases. No mutations were found analysing ALK, KIT, MET and mTOR.

Materials and Methods: Next generation sequencing (NGS) was performed in FFPE samples from 118 ATC using MiSeq (Illumina) and CLC Cancer Research Workbench (CLCbio; Qiagen) for mutation analysis in: ALK, BRAF, CDKN2A, EGFR, ERBB2, HRAS, KIT, KRAS, MET, mTOR, NRAS, PDGFRA, PI3KCA, p53, RB1, RET and TSC2. Sanger sequencing was used to detect TERT promotor mutations.

Conclusions: To our knowledge this is the largest study analysing mutations for targeted therapy of ATC. We found that 33% of ATC harbour mutations in pathways amendable to targeted therapy. Molecular screening in ATC is suggested for targeted therapies since current conventional treatment for ATC proved mainly futile.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 17300