Genomic variation associated with carcinoma showing thymus-like elements (CASTLE) in thyroid gland

Background Carcinoma showing thymus-like elements (CASTLE) is a rare kind of malignant tumor of thyroid gland. The genetic mutation characteristics of CASTLE are not clear. Methods We retrospectively analyzed seven patients diagnosed as CASTLE tumor in our hospital, and performed whole exome sequencing (WES) in five cases to analyze the genomic variation of CASTLE in thyroid gland. Results The diagnosis of CASTLE was confirmed by histopathological and immunohistochemical results. Immunohistochemical staining showed that cell membranes of tumor samples in all cases were moderately to strongly positive for CD5 and CD117. WES presented a large number of single nucleotide variants (SNVs), insertions and deletions (InDel), and copy number variations (CNVs). By comparing with the TCGA database, we found novel mutations in significantly mutated genes such as FBXL16, PAQR7, LEFTY1, UBA52, and FLNA, as well as in potential disease-related driver genes such as MLLT10, FLNA, CYLD, HLA-B, KMT2D, SFPQ, MUC16, EEF2, and KMT2C. Conclusions CASTLE tumors contain unique tumor driver gene mutations. The information about mutations in several novel genes obtained in this study may contribute to unraveling the molecular mechanisms responsible for the emergence of thyroid CASTLE tumors and help formulating possible in-roads for treatment.