Genomic Differences in Thyroid Cancers From Primary Sites Versus Distant Metastases in Individual Patients: A Clinical Perspective and Preliminary Report

Yen-Bo Lin ¹, Hsiang-Wei Hu ², An-Ko Chung ³

¹Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan.
²Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
³Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan.
⁴Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁵Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
⁶Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
⁷Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁸Department of Oncology, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan.
⁹Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan.
¹⁰Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
¹¹Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
¹²Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
¹³Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹⁴Division of Thoracic Surgery, Department of Surgery, National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁵Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliu City, Taiwan.
¹⁶Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

⁰Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan.

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February 12, 2025

View abstract on PubMed

Summary

Genetic differences between primary thyroid cancer and its metastases vary significantly. Analyzing multiple tumor samples provides crucial insights for personalized cancer treatment strategies.

Area Of Science

Oncology
Genetics
Molecular Biology

Background

Distant metastasis is a primary driver of thyroid cancer mortality.
Limited genetic profiling of single tumor samples hinders understanding of cancer evolution.
Intra-patient genetic differences between primary tumors and metastases remain largely uncharacterized.

Purpose Of The Study

To investigate the genetic discrepancies between primary thyroid tumors and their distant metastases.
To identify novel genetic alterations in advanced thyroid cancer.
To assess the clinical implications of intra-patient genetic heterogeneity.

Main Methods

Recruitment of patients with thyroid cancer and distant metastasis.
Comprehensive genetic analysis using a thyroid cancer-specific next-generation sequencing (NGS) panel.
Analysis of 66 specimens from 29 patients, including primary tumors and metastatic sites.

Main Results

Identified 16 mutations and 4 fusions, including two novel fusions (FGFR2-SHTN1 and RFTN1-BRAF).
Observed genetic discrepancies between primary and metastatic sites in 31% of patients, often involving additional oncogenic alterations (89%).
Found a significant association between longer time intervals between specimen collection and genetic discrepancies (p=0.032).

Conclusions

Genetic alterations in thyroid cancer exhibit significant heterogeneity between primary and metastatic sites.
The observed patterns of genetic discrepancies provide valuable insights for clinical decision-making.
Multi-sample genetic profiling is essential for understanding thyroid cancer progression and guiding treatment.

Keywords:

fusion genes metastasis mutations oncogene thyroid cancer

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