BRAF ^wild papillary thyroid carcinoma has two distinct mRNA expression patterns with different clinical behaviors

Background: Using a large set of genomic data from The Cancer Genome Atlas (TCGA), we classified BRAF ^wild papillary thyroid carcinomas (PTCs) into 2 subtypes with distinct molecular patterns and different clinical behaviors. We also suggested gene signatures (RAS-score) to predict molecular subtypes and clinical behaviors of BRAF ^wild PTC. Method: Integrated genomic analysis was done using all genomic data of PTC in TCGA data portal (https://tcga-data.nci.nih.gov) and cancer browser (https://genome-cancer.ucsc.edu). Using Gene Ontology and a logistic regression test, we selected gene signatures (RAS-score) and applied this prediction model to the validation cohort (GSE60542). Result: When we performed multiplatform genomic analysis, BRAF ^wild PTCs were divided into 2 molecular subtypes. Each subtype showed distinct molecular patterns and clinical behaviors. Gene signatures successfully predicted molecular subtype in another validation cohort. Conclusion: We found that BRAF ^wild PTCs were divided into 2 molecular subtypes and each subtype showed distinct molecular patterns, different activated pathways, and different clinical behaviors.