Genomic profiling of lymph node and distant metastases from papillary and poorly differentiated thyroid carcinomas

Abstract Purpose: To perform a molecular profiling of the metastases from papillary thyroid carcinomas (PTCs) and poorly differentiated thyroid carcinomas (PDTCs). Methods: We retrieved and analyzed the molecular and clinical features of 136 metastases from PTCs and 35 metastases from PDTCs subjected to targeted DNA sequencing, from cBioPortal. The clinicopathological data included the number and location of the metastases, and genomic data included mutations, translocations, copy number alterations and fraction of the genome altered (FGA). Results: Bone metastases from PTCs had a lower frequency of BRAF mutations than the lymph node metastases (LNMs) (43% vs 88%, pRBM10 and NRAS mutations than the LNMs (21% vs 3% for both, pRETtranslocations was higher in the lung metastases from PTCs than the LNMs (15% vs 3%, pTERTpromoter mutations than the LNMs from patients harboring less than 4 DMs (96% vs 65%, pSDHA gene amplifications were enriched in the bone metastases from PDTCs and absent in the LNMs (38% vs 0%, pConclusion: Metastases from PTCs and PDTCs harbor clinically relevant alterations affecting distinct body locations, such as NRAS and RBM10 mutations, RET translocations and SDHAamplifications that may be explored therapeutically.