Recently the mutational landscape of HER-2 heterogeneous carcinomas with two separate clones have been analysed and distinct driver genetic alterations in the different components have been demonstrated suggesting that HER-2 negative components are likely driven by genetic alterations not present in the HER-2+ components, including BRF2 and DSN1 amplification and HER-2 I767M somatic mutations [22]. This evidence concerns the gene ERBB2 and carcinoma.