Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.

摘要

c-CBL (CBL) encodes a multifunctional protein engaged in the regulation of intracellular signaling pathways.(1,2) It was first identified as a cellular counterpart of the viral oncogene, v-CBL, that causes murine lymphoma.(3,4) Although no genetic evidence existed suggesting its role in human carcinogenesis, the recent discovery of c-CBL mutations in myeloid cancers has unveiled a unique oncogenic mechanism mediated by gain-of-function of a mutated tumor suppressor, closely associated with allelic conversion of 11q arms.(5-9) In this review, we summarize our current knowledge about c-CBL mutations and discuss the molecular mechanisms of their gain-of-function.