Functional pre-therapeutic evaluation by genome editing of variants of uncertain significance of essential tumor suppressor genes.

ABSTRACT:

Background

Targeted therapies in oncology are promising but variants of uncertain significance (VUS) limit their use for clinical management and necessitate functional testing in vitro. Using BRCA1 and BRCA2 variants, which have consequences on PARP inhibitor sensitivity, and POLE variants, potential biomarkers of immunotherapy response, we developed a rapid functional assay based on CRISPR-Cas9 genome editing to determine the functional consequences of these variants having potentially direct implications on patients' access to targeted therapies.

Methods

We first evaluated the functional impact of 26 BRCA1 and 7 BRCA2 variants by editing and comparing NGS results between the variant of interest and a silent control variant. Ten of these variants had already been classified

SUBMITTER: Billaud A 

PROVIDER: S-EPMC8576946 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature