Mutated axon guidance gene PLXNB2 sustains growth and invasiveness of stem cells isolated from Cancers of Unknown Primary

ABSTRACT: The genetic changes sustaining the development of Cancers of Unknown Primary (CUP) remain elusive. The whole-exome genomic profiling of 14 rigorously selected CUP samples did not reveal specific recurring mutation in known driver genes. However, by comparing the mutational landscape of CUPs with that of most other human tumor types, it emerged a consistent enrichment of changes in genes belonging to the axon guidance KEGG pathway. In particular, G842C mutation of PlexinB2 (PlxnB2) was predicted to be activating. Indeed, knocking down the mutated, but not the wild-type, PlxnB2 in CUP stem cells resulted in the impairment of self-renewal and proliferation in culture, as well as tumorigenic capacity in mice. Conversely, the genetic transfer of G842C-PlxnB2 was sufficient to promote CUP stem c

SUBMITTER: Dr. Serena Brundu 

PROVIDER: S-SCDT-10_15252-EMMM_202216104 | biostudies-other |

REPOSITORIES: biostudies-other