Genomic profiling of primary and metastatic thyroid cancers

in Endocrine-Related Cancer
Authors:
Valdemar Máximo i3S Instituto de Investigação e Inovação em Saúde, Porto, Portugal
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

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Miguel Melo i3S Instituto de Investigação e Inovação em Saúde, Porto, Portugal
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitário de Coimbra, Medical Faculty, University of Coimbra, Coimbra, Portugal

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Yingjie Zhu Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, USA

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Andrea Gazzo Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, USA

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Manuel Sobrinho Simões i3S Instituto de Investigação e Inovação em Saúde, Porto, Portugal
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal
Department of Pathology, Hospital São João, Porto 4200-319, Portugal

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Arnaud Da Cruz Paula i3S Instituto de Investigação e Inovação em Saúde, Porto, Portugal
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

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https://orcid.org/0000-0001-7694-8760
, and
Paula Soares i3S Instituto de Investigação e Inovação em Saúde, Porto, Portugal
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

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https://orcid.org/0000-0001-9607-6998

Correspondence should be addressed to A Da Cruz Paula: arnaud.paula@i3s.up.pt

*(A Da Cruz Paula and P Soares contributed equally to this work)

DOI:
https://doi.org/10.1530/ERC-23-0144
Volume/Issue:
Volume 31: Issue 2
Article Type:
Research Article
Article ID:
e230144
Online Publication Date:
11 Jan 2024
Copyright:
© the author(s) 2024
Restricted access
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The genetic repertoire of primary thyroid cancers (TCs) is well documented, but there is a considerable lack of molecular profiling in metastatic TCs. Here, we retrieved and analyzed the molecular and clinical features of 475 primary and metastatic TCs subjected to targeted DNA sequencing, from the cBioPortal database. The cohort included primary and metastatic samples from 276 papillary thyroid carcinomas (PTCs), 5 follicular thyroid carcinomas, 22 Hürthle cell carcinomas (HCCs), 127 poorly differentiated thyroid carcinomas (PDTCs), 30 anaplastic thyroid carcinomas (ATCs) and 15 medullary thyroid carcinomas. The ATCs had the highest tumor mutational burden and the HCCs the highest fraction of the genome altered. Compared to primary PTCs, the metastases had a significantly higher frequency of genetic alterations affecting TERT (51% vs 77%, P < 0.001), CDKN2A (2% vs 10%, P < 0.01), RET (2% vs 7%, P < 0.05), CDKN2B (1% vs 6%, P < 0.05) and BCOR (0% vs 4%, P < 0.05). The distant metastases had a significantly lower frequency of BRAF (64% vs 85%, P < 0.01) and a significantly higher frequency of NRAS (13% vs 3%, P < 0.05) hotspot mutations than the lymph node metastases. Metastases from HCCs and PDTCs were found to be enriched for NF1 (29%) and TP53 (18%) biallelic alterations, respectively. The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, P < 0.01) and PDTCs (43% vs 22%, P < 0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.

Supplementary Materials

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Sept 2018 onwards Past Year Past 30 Days
Full Text Views 118 118 5
PDF Downloads 139 139 8

 

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2024
Article ID:
e230144
Received Date:
15 May 2023
Accepted Date:
28 Nov 2023
Print Publication Date:
01 Feb 2024
Online Publication Date:
11 Jan 2024
Keywords:
thyroid cancers; DNA sequencing; somatic mutations; copy number alterations; distant metastasis

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