Abstract
RB1 was the first identified tumour suppressor gene, named for its crucial role in opposing retinoblastoma oncogenesis. The RB1 gene encodes the retinoblastoma protein pRB, which is a well-known negative regulator of the cell cycle. However, pRB also contributes to cell differentiation by restricting reprogramming and stem cell properties. Accordingly, RB1 inactivation in tumours can induce phenotypic modifications, contributing to tumour progression. Indeed, RB1 pathogenic alterations, either point mutations or deletions, leading to pRB loss of function are observed in 5% of all human cancers. Mutations are much more prevalent in some histologic subgroups, including retinoblastoma, spindle cell lipoma, neuroendocrine prostate cancer and small cell lung carcinoma. In such entities, molecular investigation of tumour samples and mechanistic studies strongly suggest that early RB1 inactivation contributes not only to dysregulation of cell cycle control, but also to the tumour cell phenotype. Among skin carcinomas, RB1 inactivation is the hallmark of primary cutaneous neuroendocrine carcinoma commonly known as Merkel cell carcinoma (MCC), but it has also been described in other tumours including a subset of squamous cell carcinomas, sebaceous carcinomas and the recently described Wnt/beta-catenin-activated non-pilomatrical carcinomas. In this context, we provide a brief overview of the contribution of RB1 inactivation to oncogenesis and tumour cell phenotypes in general and summarise current knowledge regarding RB1-deficient cutaneous carcinomas, highlighting the potential uses of RB1 pathway characterisation for diagnosis, prognosis and therapeutic purposes.