In the 15 tumours with p.S1344L in the RNase IIIa domain, there were 4 Wilms tumours, 4 malignant melanomas, 1 Merkel cell carcinoma, 3 endometroid carcinomas, 2 colorectal cancers and 1 cholangiocarcinoma.10 12–15 Tumours bearing RNase IIIa-S1344L hotspot mutations are most commonly malignant melanomas (4/15; 27%) in contrast to tumours bearing hotspot mutations in the RNase IIIb domain (2/318; 0.6%).4 15 This indicates that hotspot mutations in different RNase III domains of DICER1 cause tissue-specific susceptibilities to develop certain tumours. The gene discussed is DICER1; the disease is neoplasm.