Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers

Jin-Ying Lu; Wern-Cherng Cheng; Kuen-Yuan Chen; Chia-Chi Lin; Ching-Chung Chang; Kuan-Ting Kuo; Pei-Lung Chen

doi:10.1016/j.jfma.2017.05.007

Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers

J Formos Med Assoc. 2018 Jun;117(6):488-496. doi: 10.1016/j.jfma.2017.05.007. Epub 2017 Jul 27.

Authors

Jin-Ying Lu¹, Wern-Cherng Cheng², Kuen-Yuan Chen³, Chia-Chi Lin⁴, Ching-Chung Chang⁵, Kuan-Ting Kuo⁶, Pei-Lung Chen⁷

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: jylu@ntu.edu.tw.
² Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
³ Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
⁴ Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan.
⁵ Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; Department of Internal Medicine, China Medical University, Taichung 404, Taiwan.
⁶ Department of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. Electronic address: pathologykimo@gmail.com.
⁷ Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei 100, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei 100, Taiwan. Electronic address: paylong@ntu.edu.tw.

PMID: 28757314
DOI: 10.1016/j.jfma.2017.05.007

Abstract

Background/purpose: Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumor's genetic information.

Methods: We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing.

Results: We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers.

Conclusion: The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers.

Keywords: Fatal thyroid cancer; Genetics; MET; MLH1; PDGFRA.

MeSH terms

Aged
Aged, 80 and over
Carcinoma / genetics*
Carcinoma / pathology
DNA Mutational Analysis / methods*
Death
Female
High-Throughput Nucleotide Sequencing
Humans
Iodine Radioisotopes
Male
Middle Aged
Mutation*
Taiwan
Thyroid Neoplasms / genetics*
Thyroid Neoplasms / pathology

Substances

Iodine Radioisotopes