Thyroid cancer phenotypes associated with RBM10 mutations. (A) Frequency of RBM10 mutations in histological subtypes of thyroid cancer samples from MSK clinical cohort (n = 737) sequenced by MSK-IMPACT and PTC from TCGA (n = 496). PTC, HGFCTC, and ATC. (B) Proportion of RBM10 mutation in non-anaplastic (PTC + HGFCTC) thyroid cancers from MSK-IMPACT and TCGA showing association of RBM10 mutation in patients with distant metastases; two-sided Fisher’s exact t test (***P < 0.0001). (C) Diagram of Hras, Rbm10, and EYFP transgenes in the mouse model. In the presence of Tpo-Cre, YFP, and mutant Hras are expressed, and Rbm10 is inactivated in thyrocytes. (D) Western blot showing Rbm10 expression in mouse thyroid lysates from the indicated genotypes. (E) Thyroid volume measurement by ultrasound of 25-wk-old mice for the indicated genotypes; the data represent mean with SD, each dot represents one mouse; statistical difference versus WT were analyzed using unpaired t test and is indicated as **P < 0.01; ns: not significant. (F) Low- (top) and high-power (bottom) magnification of H&E-stained thyroids of the indicated genotypes showing representative histology. (G) H&E-stained sections of thyroid cancer metastases to lung from a TEHR mouse; low (left) and high magnification (right). Source data are available for this figure: SourceData F1.