A little pRB can lead to big problems.

Germline deletion of RB1, the gene encoding the retinoblastoma tumor-suppressor protein pRB, predisposes to eye tumor formation upon loss of the remaining wild-type allele. Many functions affecting cell-cycle control, cell-cycle exit, and numerous other processes involved in the transformed phenotype have been ascribed to pRB, and deregulation of these processes is generally thought to result from complete loss of pRB in both hereditary and sporadic tumors in multiple tissues. Loss of just one allele of RB1 is now shown to lead to replication stress and aneuploidy in both mouse and human cells, and the mechanism through which this haploinsufficient phenotype is achieved may open up new opportunities for interceding both in tumor initiation and in treatment of extant tumors.