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Endocrine Abstracts (2015) 37 GP24.03 | DOI: 10.1530/endoabs.37.GP.24.03

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1Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic; 2Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; 3Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; 4Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.


Objectives: Although, almost all patients with inherited medullary thyroid carcinomas (MTC) harboured RET proto-oncogene mutation, in patients with sporadic MTC, mutations in RET are detected only in half of cases. Thus still unknown genetic causes are responsible for half of sporadic MTC and it is necessary to search for another mutations.

Methods: DNAs from fresh frozen thyroid tissues of 27 sporadic MTC were extracted. The next-generation sequencing (NGS) approach was used to target 175 exonic regions of 26 genes involved in tumors. The samples were prepared using a TruSight Tumor panel (Illumina) and sequenced with a MiSeq sequencer (Illumina). Analysis of variants was performed by MiSeq Reporter Software and evaluated by Illumina VariantStudio Software. RET and HRAS genes were analysed separately using direct sequencing by CEQ 8000 (Beckman Coulter), because these two genes were not included in the panel.

Results: RET mutations were detected in 12 samples – mutation in exon 16 (Met918Thr) in eight patients and mutations in exon 10 and 11 (Cys618Ser, Cys620Ser, Cys630Ser, and 628–632del) in four patients. In four MTC tissues mutations in HRAS genes (codons 13 and 61) were detected. NGS revealed mutations in KRAS gene in codons 12 and 61 in three MTC patients. Futher, we identified missense mutation Thr273Asn in gene for hepatocyte growth factor receptor (MET) in the patient with mutation Gln61Arg in HRAS gene. Except this patient all mutations were presented exclusively.

Conclusions: In our cohort of sporadic MTC tissues, mutations were detected in 19 patients (70.3%) – RET mutations in 44.4% and RAS mutations in 25.9%. Except of known mutations in RET and RAS genes, the unknown variant in conserved sequence of MET gene was revealed which was identified as deleterious and possibly damaging in software SIFT and PolyPhen-2 respectively.

Disclosure: This work was supported by IGA MH CR (grant number NT13901-4) and MH CR (grant number DRO 00023761).

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