Endocrine Abstracts

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.