Genomic landscape of papillary thyroid carcinoma in Kuwait reveals novel candidate somatic variants

Abstract Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy and is increasingly diagnosed in the Middle East, including Kuwait. To characterize its genomic landscape, targeted next-generation sequencing was performed on 72 histologically confirmed PTC tumors collected between 2019 and 2022. DNA from FFPE samples was analyzed using a high-depth cancer gene panel with standardized pipelines for variant calling, annotation, and pathogenicity filtering. The cohort (median age 46.5 years) was predominantly female and largely presented with early-stage disease. Across all tumors, 227 somatic variants were identified, with low tumor mutational burden (median 4.56 mut/Mb). Canonical drivers were frequent, including BRAF V600E (54.2%) and recurrent RAS Q61 mutations. Rare, previously unreported candidate variants were detected in BCOR , STAG2 , PTPRT , and ARID1A . In silico modeling indicated modest protein-stability effects requiring experimental validation. These results broaden the candidate PTC mutational spectrum and emphasize the importance of genomic profiling in understudied populations.