Fig. 1
Survey of DICER1 cancer mutations reveals recurrent RNase IIIb and IIIa hotspots. a Lollipop mutation diagrams of TCGA-PanCan (pointing up) and MSK-IMPACT (pointing down) datasets. The sites labeled in black designate mutations in the four catalytic residues in the RNase IIIb domain (D1709, E1705, E1813, D1810, in black) and an adjacent residue (G1809, in green) that are the major known biallelic DICER1 events in cancer. These aggregate data also reveal an uncharacterized biallelic alteration involving S1344L (in red) in the RNase IIIa domain. The background of other somatic mutations of unknown functional significance is shown for perspective; certain other apparently recurrent mutations are recovered in both TCGA and IMPACT datasets (e.g., PAZ-R944Q, in gray), but were not associated with biallelic hits in non-hypermutated samples. b Left column, examples of biallelic hits in each of the five known RNase IIIb hotspot residues in IMPACT data, with their corresponding secondary inactivating mutations and cancer types. Right column, a selection of multiple cancer types that exhibit RNase IIIa-S1344L and carry diverse secondary inactivating mutations across TCGA and IMPACT data. Patient sequencing from metastatic tumors are noted (in blue)
