RB1 and neoplasm: Two mutational events following a loss of immune surveillance appear critical to cancer development in MCC patients; firstly, MCV is clonally integrated in an apparently unbiased location in the tumour genomes, and, secondly, the TAg helicase domain associated with NCCR binding and thus viral (lytic) replication is abolished; however, all mutations downstream of the LXCXE Rb tumour suppressor-binding motif are retained [4, 229].