Genetic and clinical profiles of 160 papillary thyroid cancers with lateral neck lymph node metastasis

Abstract

BackgroundLymph node metastasis is widespread in papillary thyroid cancer (PTC). Patients are more vulnerable than those with central lymph node metastasis if they have lateral neck lymph node metastasis (LLNM). There are few researches focus on the correlation between clinical characteristics and genetic profile of PTC with LLNM. In this study, we aimed to analyze the clinical and genetic features of PTC with LLNM.MethodsA total of 160 primary tumor samples derived from PTC patients with LLNM were involved. Targeted next-generation sequencing was carried out on all samples with 57 known thyroid-cancer-related genes. The associations between genomic alternations and clinical characteristics of PTC with LLNM were statistically evaluated.ResultsThe median age of patients was 37 years, ranging from 5 to 77 years and the female/male ratio was 1.86. The most frequently altered genes in our series were BRAF mutation (68%), followed by RET fusion (17%), TERT promoter mutation (5%) and PIK3CA mutation (2%). To be noted, all PTC patients with LLNM of TERT promoter mutations appeared along with BRAF mutations (8/8) and half of them experienced a relapse. Intriguingly, we found more metastatic lymph nodes in patients with RET fusion, but there was no statistically significant difference in metastatic lymph node ratio than those with BRAF mutation or without mutation. A high rate of gene fusion (70%) was found in the pediatric population, with aggressive late-onset disease.ConclusionsPTC patients with LLNM is characterized by a high rate of BRAF mutation. Due to the observed clinicopathological differences in those patients among different alterations, further prospective studies are needed to verify our results and to evaluate the most suitable treatment strategies.

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

“…Within the metastatic setting however, the molecular characterization of the metastases from distinct body locations in patients with PTCs and PDTCs is rather scarce. A recent study has focused on the molecular analysis of 160 PTC patients with lateral neck lymph node metastasis (LNMs), and noticed a high frequency of BRAF mutations (68%), followed by RET translocations (17%) and TERT promoter mutations (5%) [3]. An additional genetic study of 8 PTC patients with symptomatic bone metastases revealed a high frequency of TERT promoter mutations (88%) and RAS mutations (50%) affecting these patients [4].…”

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

“…The B-Raf proto-oncogene ( BRAF ) encodes a cytoplasmic serine/threonine kinase with a key role in regulating the mitogen-activated protein kinase signal transduction pathway [ 9 ]. The BRAF V600E mutation in exon 15 of the BRAF gene has been studied in different cancers, including thyroid cancers [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Induction of the BRAF V600E mutation in thyroid cells may lead to frequent hypermethylation [ 21 ].…”

“…The BRAF V600E mutation is common in thyroid cancer [ 13 , 15 , 16 , 18 , 22 , 23 , 25 ], as is DNA methylation [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. However, the interaction or association between them is not well-studied.…”