Role of CBL Mutations in Cancer and Non-Malignant Phenotype

SIMPLE SUMMARY: CBL mutations are progressively being described as involved in different clinical manifestations. Somatic CBL mutations can be found in different type of cancer. The clinical spectrum of germline mutations configures the so-called CBL syndrome, a cancer-predisposing condition that includes multisystemic involvement characterized by variable phenotypic expression and expressivity. In this review we provide an up-to-date review of the clinical manifestation of CBL mutations and of the molecular mechanisms in which CBL exerts its pathogenic role. ABSTRACT: CBL plays a key role in different cell pathways, mainly related to cancer onset and progression, hematopoietic development and T cell receptor regulation. Somatic CBL mutations have been reported in a variety of malignancies, ranging from acute myeloid leukemia to lung cancer. Growing evidence have defined the clinical spectrum of germline CBL mutations configuring the so-called CBL syndrome; a cancer-predisposing condition that also includes multisystemic involvement characterized by variable phenotypic expression and expressivity. This review provides a comprehensive overview of the molecular mechanisms in which CBL exerts its function and describes the clinical manifestation of CBL mutations in humans.