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

Yen-Bo Lin; Hsiang-Wei Hu; An-Ko Chung; Jin-Ying Lu; Wan-Chen Wu; I-Hsuan Chiu; I Chu; Chia-Chi Lin; Jih-Hsiang Lee; Feng-Jung Nien; Kuen-Yuan Chen; Ming-Hsun Wu; Chun-Nan Chen; Chun-Wei Wang; Ting-Chun Kuo; Chia-Hung Lin; Mei-Fang Cheng; Wei-Yih Chiu; Shuenn-Wen Kuo; Wen-Hui Hsih; Chih-Yuan Wang; Wei-Shiung Yang; Pei-Lung Chen; Shyang-Rong Shih

doi:10.1002/hed.28100

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

Head Neck. 2025 Jul;47(7):1907-1927. doi: 10.1002/hed.28100. Epub 2025 Feb 12.

Authors

Yen-Bo Lin¹, Hsiang-Wei Hu², An-Ko Chung³, Jin-Ying Lu⁴, Wan-Chen Wu⁴, I-Hsuan Chiu⁵, I Chu⁶, Chia-Chi Lin⁷, Jih-Hsiang Lee^{7

8}, Feng-Jung Nien⁹, Kuen-Yuan Chen¹⁰, Ming-Hsun Wu¹⁰, Chun-Nan Chen¹¹, Chun-Wei Wang¹², Ting-Chun Kuo¹⁰, Chia-Hung Lin⁴, Mei-Fang Cheng¹³, Wei-Yih Chiu⁴, Shuenn-Wen Kuo¹⁴, Wen-Hui Hsih¹⁵, Chih-Yuan Wang^{4

6}, Wei-Shiung Yang^{6

16}, Pei-Lung Chen^{3

4

5}, Shyang-Rong Shih^{4

6}

Affiliations

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

PMID: 39936351
DOI: 10.1002/hed.28100

Abstract

Background: Distant metastasis is a leading cause of thyroid cancer (TC)-related deaths. Genetic profiling is typically limited to one sample per patient due to cost and sampling-risk concerns. Differences between samples from thyroid and distant metastasis within individual patients are unclear.

Methods: Patients with TC and distant metastasis were recruited for genetic analysis.

Results: Using a TC-specific NGS panel, 66 specimens from 29 patients were analyzed, identifying 16 mutations and 4 fusions, including two novel fusions (FGFR2-SHTN1 and RFTN1-BRAF). Genetic alterations differed between primary and metastatic sites in nine patients (31%), predominantly in additional oncogenic alterations (89%). More genetic alterations were found at the primary site in three patients and metastatic sites in four. Distinct mutations were found in two patients. A longer time interval between specimen acquisitions was significantly associated with genetic discrepancies (p = 0.032).

Conclusion: Patterns of genetic discrepancies between primary and metastatic TC vary, offering valuable insights for clinical practice.

Keywords: fusion genes; metastasis; mutations; oncogene; thyroid cancer.

MeSH terms

Adult
Aged
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasm Metastasis / genetics
Thyroid Neoplasms* / genetics
Thyroid Neoplasms* / pathology

Abstract

MeSH terms

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