Abstract
BackgroundThe objective of this study was to investigate genetic variations and the relationships between these genetic variations and clinicopathological features of high-recurrence risk papillary thyroid carcinoma in a southern Chinese population.MethodsOne hundred sixty-eight patients of high-recurrence risk papillary thyroid carcinoma were recruited for this study from 2017 to 2018. Formalin-fixed paraffin-embedded tissue and the data of clinicopathological characteristics were all collected and analyzed from these patients. We used next-generation sequencing technology to investigate the targeted gene mutations and gene fusions of the pathology specimens.ResultsThe frequency of candidate tumor driver gene mutation was 85.1% in 143 patients, including BRAF V600E mutation in 119 patients(70.8%), RET fusion in 13 patients(7.7%), TERT promoter mutations in 11 patients(6.5%), RAS (HRAS, NRAS, KRAS) gene mutations in 10 patients(6.0%), and other mutations involving TP53, PIK3CA, AKT1, PTEN and NTRK1. Concomitant presence of more than two genetic aberrations was seen in 27 patients (16.1%). Our study showed that BRAF V600E mutation is highly correlated with conventional PTC (p < 0.001), BRAF V600E and TERT promoter mutation duet was associated with older patient age (> 45, p = 0.003) and higher disease stage of III or IV (p = 0.002). RAS gene and BRAF V600E co-mutations were only seen in multifocal PTC (p = 0.015).ConclusionIn our high-recurrence risk PTC cohort, most patients had more than one driver gene aberration. Coexistence of BRAF V600E with TERT promoter mutations or with RAS mutations were significantly correlated with worse clinicopathological characteristics.
Highlights
The incidence of thyroid cancer has increased throughout the world in the last few decades [1]
Most of the Papillary thyroid cancer (PTC) patients were diagnosed with conventional PTC (92.9%, 156/168), the remaining patients were diagnosed with follicular variant PTC (7.1%, 12/168)
We found that B-type Raf kinase (BRAF) V600E alone and co-mutations status of BRAF + Telomerase reverse transcriptase (TERT), BRAF + RAS showed correlation with age, disease stage and lesion number (Table 4)
Summary
The incidence of thyroid cancer has increased throughout the world in the last few decades [1]. Recurrence remains relatively common, for invasive PTC and cancer with BRAF V600E mutation [4]. The most common mutations in PTC, including BRAF point mutations, RAS point mutations, and RET gene rearrangements, perturb cell signaling in the mitogenassociated protein kinase (MAPK) pathway, leading to inappropriate cell growth and survival [6]. BRAF V600E mutation has been associated with more aggressive tumor characteristics, such as capsular invasion, lymph node metastasis, distal metastasis and recurrence [8]. Mutations in PI3K/AKT pathway genes such as PIK3CA, and tumor suppressor genes such as TP53 and PTEN have been identified in PTC, indicating complex genetic aberrations disturbing cellular growth and survival signals and contributing to the pathogenesis of PTC [10]. The objective of this study was to investigate genetic variations and the relationships between these genetic variations and clinicopathological features of high-recurrence risk papillary thyroid carcinoma in a southern Chinese population
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