Genomic profiling of metastases from papillary and poorly differentiated thyroid carcinomas

Cruz Paula Arnaud Da; Valdemar Maximo; Miguel Melo; Manuel Sobrinho-Simoes; Paula Soares

doi:10.1530/endoabs.101.PS2-15-03

PS2-15-03

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Endocrine Abstracts (2024) 101 PS2-15-03 | DOI: 10.1530/endoabs.101.PS2-15-03

ETA2024 Poster Presentations Translational thyroid cancer research-1 (10 abstracts)

Genomic profiling of metastases from papillary and poorly differentiated thyroid carcinomas

Arnaud Da Cruz Paula ¹ , Valdemar Maximo ² , Miguel Melo ³ , Manuel Sobrinho-Simões ⁴ & Paula Soares ⁵

Err

Author affiliations

¹Ipatimup, Cancer Signalling & Metabolism, Cancer Signalling & Metabolism, Porto, Portugal; ²Department of Pathology of Medical Faculty of University of Porto, Instituto de Investigação e Inovação Em Saúde Da Universidade Do Porto, Cancer Signalling and Metabolism Research Group, Porto, Portugal; ³I3s, Ipatimup, Chuc, Coimbra, Portugal; ⁴University Hospital of São João, Medical Faculty and Institute of Molecular Pathology and Immunology, University of Porto, X, Portugal; ⁵Medical Faculty University of Porto, Ipatimup, Cancer Signaling and Metabolism Group, Porto, Portugal

Objective: While the genetic repertoire of papillary thyroid carcinomas (PTCs) and poorly differentiated thyroid carcinomas (PDTCs) is well documented, there is a considerable lack of molecular profiling in the metastases of these tumors. Hence, we aim at performing a meticulous molecular profiling of metastatic PTCs and PDTCs.

Methods: We retrieved and analyzed the molecular and clinical features of 136 metastatic PTCs and 33 metastatic PDTCs subjected to targeted DNA sequencing, from the cBioPortal database. The clinicopathological data included the number and location of the metastases, and relevant genomic data included somatic mutations, structural variants, copy number amplifications and homozygous deletions, tumor mutational burden and fraction of the genome altered (FGA).

Results: Bone metastases from PTCs had a significantly lower frequency of BRAF hotspot mutations than the lymph node metastases (LNMs) (43% vs 85%, P < 0.01) and head and neck metastases (43% vs 89%, P < 0.05), and a significantly higher frequency of RBM10 and NRAS mutations than the LNMs (21% vs 3% for both genes, P < 0.05). In addition, the FGA of the bone metastases was found to be significantly higher when compared to the FGA of the head and neck, and lung metastases (5.6% vs 0.1% and 5.6% vs 1.3%, P < 0.05, respectively). The frequency of RET translocations was significantly higher in the lung metastases from PTCs when compared to the LNMs (15% vs 4%, P < 0.05). The LNMs from PTC patients harboring ≥4 distant metastases (DMs) had a significantly higher frequency of TERT promoter and ATM pathogenic mutations than the LNMs from PTC patients harboring <4 DMs (95% vs 63%, P < 0.001, and 13% vs 0%, P < 0.05, respectively). Moreover, copy number amplifications affecting SDHA were significantly more frequent in the bone metastases from PDTCs when compared to the LNMs (38% vs 0%, P < 0.05).

Conclusion: The metastases from PTCs and PDTCs harbor clinically relevant alterations associated to distinct body locations, such as BRAF and RBM10 mutations, RET translocations and SDHA amplifications that may be explored therapeutically.