Next generation sequencing based detection of 15 target genes mutations in papillary thyroid carcinoma

Abstract

ObjectivesNext generation sequencing (NGS) method provided a valuable tool for a comprehensive understanding of papillary thyroid carcinoma (PTC) biology. We explored the application of NGS based detection for a panel of 15 target genes mutations and analyzed the gene spectrum in PTC.MethodsA total of 211 formalin‐fixed, paraffin‐embedded (FFPE) tissue specimens from surgically removed PTC samples were collected and detected with 15 target genes by NGS.ResultsIn general, 181 mutations of all types of 15 target genes were detected in 164 samples (77.73% of 211 samples). There were 22.27% samples with no mutation, and 70.14% samples carried mutations in single gene. A total of 7.11% samples simultaneously harboured two gene mutations and 0.47% sample carried triple different gene mutations. The BRAF mutation was the most common mutation type, followed by TERT, RET fusion, TP53, PIK3CA, GNAS, NTRK1 fusion, CTNNB1, NRAS, and HRAS. TSHR, AKT1, PETN, KRAS, and PAX8 mutations were negative among PTC patients. All point mutations found in PTC samples were heterozygous mutations with allelic frequency ranged from 1.12% to 48.04% of alleles. The fusion mutations showed the percent of reads ranged from 2.30% to 55.54%. For samples with carried two mutations, the allelic frequency of mutations was similar. However, for the sample harboured triple gene mutations, the allelic frequency of NRAS mutation was similar to TERT mutation (33.62%‐39.67%) and TP53 mutation showed much lower abundance (4.13%).ConclusionsNGS‐based detection method showed advantages in detecting multiple gene mutations simultaneously, economically and efficiently, and providing quantitative assessment of mutation frequency using targeted sequencing panel. It can improve the accuracy of diagnosis and prognostication and is useful for providing personalized treatments for PTC patients.