Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype.

ABSTRACT:

Purpose

Much of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach.

Methods

Whole-genome copy-number findings in patients with melanoma predisposition syndrome congenital melanocytic nevus were extrapolated to a sporadic melanoma cohort. Functional effects of duplications in PPP2R3B were investigated using immunohistochemistry, transcriptomics, and stable inducible cellular models, themselves characterized using RNAseq, quantitative real-time polymerase chain reaction (qRT-PCR), reverse phase protein arrays, immunoblotting, RNA interference, immunocytochemistry, proliferation, and migration assays.

Results

We identify here a previously unreported genetic susceptibility to melanoma and melano

SUBMITTER: Polubothu S 

PROVIDER: S-EPMC8460442 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature