SMAD4 and cancer: Previously reported SV hotspots in MSS primary cancers included deletions (for example, APC, PTEN, SMAD4 and TP53), amplifications (for example, IGF2, MYC and RASL11A regulatory element) and fusions (for example, EIF3E–RSPO2 and PTPRK–RSPO3)4,7,8,21.