The Clinical and Molecular Features in the VHL Renal Cancers; Close or Distant Relatives with Sporadic Clear Cell Renal Cell Carcinoma?

SIMPLE SUMMARY: VHL syndrome is an autosomal dominant hereditary cancer syndrome and one of the leading causes of death is ccRCC. Current target therapies may lead to stable disease or partial remission, as best response and scant evidence supports the therapeutic decision-making in metastatic ccRCC. Therefore, new genetic and epigenetics insights are needed, to guide the development of more effective target therapies and to promptly predict the presence and prognosis of ccRCC. Our review highlights all the new molecular perspectives based on research of genetic alterations, biological pathways and promising biomarkers in the VHL-associated hereditary ccRCC. ABSTRACT: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome caused by germline mutations in the VHL tumor suppressor gene, characterized by the susceptibility to a wide array of benign and malign neoplasms, including clear-cell renal cell carcinoma. Moreover, VHL somatic inactivation is a crucial molecular event also in sporadic ccRCCs tumorigenesis. While systemic biomarkers in the VHL syndrome do not currently play a role in clinical practice, a new promising class of predictive biomarkers, microRNAs, has been increasingly studied. Lots of pan-genomic studies have deeply investigated the possible biological role of microRNAs in the development and progression of sporadic ccRCC; however, few studies have investigated the miRNA profile in VHL patients. Our review summarize all the new insights related to clinical and molecular features in VHL renal cancers, with a particular focus on the overlap with sporadic ccRCC.