Abstract
Genetic and epigenetic alterations are associated with the progression and prognosis of medullary thyroid carcinoma (MTC). We performed whole-exome sequencing of tumor tissue from seven patients with sporadic MTC using an Illumina HiSeq 2000 sequencing system. We conducted Sanger sequencing to confirm the somatic mutations in both tumor and matched normal tissues. We applied Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis with the Database for Annotation, Visualization, and Integrated Discovery and STRING for pathway analysis. We detected new somatic mutations in the BICD2, DLG1, FSD2, IL17RD, KLHL25, PAPPA2, PRDM2, PSEN1, SCRN1, and TTC1 genes. We found a somatic mutation in the PDE4DIP gene that had previously been discovered mutated in other tumors but that had not been characterized in MTC. We investigated pathway deregulation in MTC. Data regarding 1152 MTCs were assembled from the Catalogue of Somatic Mutations in Cancer (COSMIC) and seven of our patients. Ontological analysis revealed that most of the variants aggregated in pathways that included the signaling pathways of thyroid cancer, central carbon metabolism, microRNAs in cancer, PI3K-Akt, ErbB, MAPK, mTOR, VEGF, and RAS. In conclusion, we conducted wide-ranging exome-wide analysis of the mutational spectrum of MTC in Taiwan’s population and detected novel genes with potential associations with MTC tumorigenesis and irregularities in pathways that resulted in MTC pathogenesis.
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This work has been supported in part by China Medical University Hospital grant (DMR-107-100) and Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW107-TDU-B-212-123004).
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This study was approved by the Institutional Review Board of Changhua Christian Hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Chang, YS., Chang, CC., Huang, HY. et al. Detection of Molecular Alterations in Taiwanese Patients with Medullary Thyroid Cancer Using Whole-Exome Sequencing. Endocr Pathol 29, 324–331 (2018). https://doi.org/10.1007/s12022-018-9543-6
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DOI: https://doi.org/10.1007/s12022-018-9543-6