A Novel Human SDHA-Knockout Cell Line Model for the Functional Analysis of Clinically Relevant SDHA Variants.

ABSTRACT:

Purpose

SDHA mutations are the most common cause of succinate dehydrogenase (SDH)-deficient GIST. Enhanced cancer surveillance of individuals carrying a known pathogenic germline SDHA mutation has the potential to detect early-stage tumors, allowing for improved patient outcomes. However, more than 95% of the >1,000 SDHA missense variants listed in ClinVar are variants of uncertain significance. Our ability to interpret the significance of SDHA variants must improve before genetic sequencing can be utilized to its full potential.

Experimental design

SDHA variants were introduced into a clonal SDHA-knockout cell line via Bxb1-mediated recombination. SDH activity and SDHA abundance were determined for each variant, and logistic regression analysis was used to derive functional

SUBMITTER: Kent JD 

PROVIDER: S-EPMC11611653 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature