The crystal structure of the entire RB N terminal domain is not well understood but there is a suggestion that the N terminal domain is well conserved and interacts with the pocket domains.26 Because a significant number of missense mutations and exon deletions map to the N terminal domain in retinoblastoma patients, similar to our NSCLC cohort, it is possible that the mutations we observed affect an unknown critical function of RB. Here, RB1 is linked to retinoblastoma.