Genomic characterization of papillary thyroid carcinoma in Chinese Shandong population.

Abstract

e18085 Background: With the emergence of mutation-based diagnosis and therapies for patients with papillary thyroid carcinoma (PTC), molecular profiling has become an important component of care. Although next-generation sequencing (NGS) gene panels are accessible to clinicians, the key genetic alterations of PTC in Chinese Shandong population were rarely descripted. Methods: A total of 127 papillary thyroid carcinoma patients were enrolled in this cohort, including 49 (38.6%) males and 78 (61.4%) females from January 2020 to May 2022. The median age were all 48 years. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were all collected and analyzed from these patients. Somatic and germline mutations were identified including 38 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA), gene fusions and rearrangements. Results: A total of 117 out of 127 papillary thyroid carcinoma were NGS-positive (92.1%), with a high prevalence of BRAF V600E mutations (52.0%, 66/127) and MLH1 mutations (23.6%, 30/127), and a low prevalence of RAS mutations (10.2%, 13/127)， ROS1 (9.4%, 12/127). Overall, 257 somatic mutations including 249 SNVs (6 splicing, 4 stopgain, 4 frameshift，and 235 nonsynonymous), 3 fusions, 3 deletions, and 1 insertions in 38 genes were identified in the PTC samples. Gene fusions, involving the RET and NTRK1 genes, were identified in three PTCs (2.4%), including NTRK1-TPM3, NTRK1-SQSTM1 and CCDC6-RET. And the three fusions patients were all BRAF V600E-negative cases. Furthermore, in our cohort, BRAF V600E mutation carriers also owned other actionable, the most frequent one was MLH1 (34.8%), followed by RET (15.2%), ROS1 (10.6%), and ATM (10.6%). We also found that three PTC patients carried germline variants of uncertain significance, including ATM (p.L857P), MET (p.L211W) and RET (p.C515R), which are heterozygous mutations. Conclusions: We described the distinct molecular profile in the Chinese Shandong population with PTC. Most patients had at least one potentially actionable mutation, predominantly driven by BRAF V600E and MLH1 alterations. These findings may help in moving toward the more comprehensive and effective personalized treatment of papillary thyroid carcinoma in Chinese.