Abstract 2276: Comprehensive analysis of the genomic landscape of thyroid cancer

Abstract

Abstract Thyroid cancer, the most common endocrine malignancy, has a high incidence worldwide. Meanwhile, the incidence of thyroid cancer ranks first in Korea. To assess the possible influence of ethnicity on the molecular profile of thyroid cancer, we compared the genomic features of South Korean thyroid cancer with European thyroid cancer. In this study, we performed whole genome sequencing profiling (WGS) for 459 Korean thyroid cancer patients, including papillary thyroid carcinoma (PTC, n = 274), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP, n =18), follicular thyroid carcinoma (FTC, n = 16), follicular thyroid adenoma (FTA, n = 63), Hürthle cell adenoma (HCA, n = 22), and invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC, n = 19). We assessed the single nucleotide variant (SNV) and insertions and deletions using Mutect2, Varscan2, and Strelka2. For mutation signature and copy number alterations analysis, we used the Maftools and GISTIC2.0 packages, respectively. Our results revealed that most somatic mutations were similar between the Korean thyroid cancer dataset and the cancer genome atlas program (TCGA). However, the Korean cohort (1%) had a much lower NRAS mutation frequency than the TCGA cohort (8%). Mutation signature analysis showed that SBS6 and SBS2 were highly associated with the TCGA and Korean cohort. SBS6 is related to defective DNA mismatch repair, and SBS2 is characterized predominantly by CC > TT doublet base substitutions. In addition, we identified the NIFTP-specific somatic mutations such as KEAP1 and ZFP36L2. This study presents insights into the genomic landscape of Korean thyroid cancer and reveals some similarities and differences with European thyroid cancer at the molecular level. Citation Format: SooHyun Im, Jong-Lyul Park, Jae-Yoon Kim, Chan-Kwon Jung, Seon-Young Kim. Comprehensive analysis of the genomic landscape of thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2276.