Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.
c-CBL (CBL) encodes a multifunctional protein engaged in the regulation of intracellular signaling pathways. It was first identified as a cellular counterpart of the viral oncogene, v-CBL, that causes murine lymphoma. 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. In this review, we summarize our current knowledge about c-CBL mutations and discuss the molecular mechanisms of their gain-of-function.
Ogawa
Seishi
S
Cancer Genomics Project, University of Tokyo, Bunkyo-ku, Tokyo, Japan. sogawa-tky@umin.ac.jp
Sanada
Masashi
M
Shih
Lee-Young
LY
Suzuki
Takahiro
T
Otsu
Makoto
M
Nakauchi
Hiromitsu
H
Koeffler
H Philip
HP
D000818:Animals; D019046:Bone Marrow Neoplasms / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*
D050721:Proto-Oncogene Proteins c-cbl