Related Experiment Video
Updated: Feb 25, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers
Jin-Ying Lu1, Wern-Cherng Cheng2, Kuen-Yuan Chen3
1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
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.
Insights
This study analyzed genetic mutations in fatal thyroid cancers, identifying novel mutations in MET and MLH1, and a homozygous PDGFRA mutation. These findings offer insights for future targeted therapies for advanced thyroid cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Surgery and radioiodine are standard treatments for thyroid cancer.
- A significant subset of thyroid cancers are inoperable or radioiodine-refractory, leading to poor survival.
- Understanding the genetic landscape of these aggressive thyroid cancers is critical for developing new treatments.
Purpose of the Study:
- To investigate the genetic alterations in fatal thyroid cancers.
- To identify potential therapeutic targets for advanced and refractory thyroid cancer.
Main Methods:
- Genomic DNA was extracted from 22 fatal thyroid cancer specimens.
- Next-generation sequencing (Ion Torrent™ Personal Genome Machine) was used to analyze 740 mutational hotspots in 46 oncogenes.
- Results were validated using conventional direct sequencing.
Main Results:
- Twenty-one mutations across 11 oncogenes were identified in the fatal thyroid cancer samples.
- Novel mutations in MET (p.N375S) and MLH1 (p.V384D) were detected in two cases each.
- A homozygous PDGFRA (p.V824V) mutation was found in 8/22 cases, with heterozygous status in non-tumor tissue; high false positive rates for EGFR mutations were noted with the Ion Torrent technique.
Conclusions:
- Genetic profiling provides valuable insights for developing targeted therapies for advanced thyroid cancer.
- The Ion Torrent Personal Genome Machine is a useful tool for comprehensive genetic mutation screening in fatal thyroid cancers.
