An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations.

ABSTRACT: Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional screen to identify potential activating ERBB4 mutations from a randomly mutated ERBB4 expression library. Ten potentially activating ERBB4 mutations were identified and subjected to validation by functional and structural analyses. Two of the 10 ERBB4 mutants, E715K and R687K, demonstrated hyperactivity in all tested cell models and promoted cellular growth under two-dimensional and three-dimensional cultu

SUBMITTER: Chakroborty D 

PROVIDER: S-EPMC9973412 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature