SFEBES2021 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)
Queen Mary University of London, London, United Kingdom
Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remain elusive due to the rarity of these tumours and heterogeneity in patient phenotype. To address this, we have used CRISPR/Cas9 to generate a series of isogenic SDH knockout cell lines as a tool to investigate the cellular consequences of loss of specific subunits. Characterisation of these cell lines demonstrates that they recapitulate the phenotypes reported for previous SDH knockout models and tumour tissue. Transcriptomic analysis has identified differentially expressed gene signatures that are unique to SDHB knockout cells, potentially identifying mechanisms responsible for the increased risk of metastasis in SDHB- deficient tumours.