DLST
Overview
DLST (dihydrolipoamide S-succinyltransferase) encodes a component of the alpha-ketoglutarate dehydrogenase complex involved in mitochondrial metabolism. In cancer genomics, DLST has been identified as one of the top alternatively spliced transcripts driven by SF3B1 hotspot mutations in breast cancer, placing it at the intersection of RNA splicing dysregulation and metabolic reprogramming.
Alterations observed in the corpus
- DLST is among the top alternatively spliced transcripts shared across all SF3B1 hotspot mutations (K700E, R625C, R625H) in HR+ HER2- breast cancer; alternative 3’ splice site usage correlates with mutant VAF in a dose-dependent manner PMID:22158541
Cancer types (linked)
- BRCA (HR+ HER2-): Altered splicing of DLST is a convergent downstream consequence of SF3B1 driver mutations in breast cancer, identified by WES and RNA-seq across isogenic knock-in cell line models PMID:22158541
Co-occurrence and mutual exclusivity
- DLST splicing dysregulation co-occurs with SF3B1 mutations and is shared with GCC2, TMEM14C, and ENOSF1 as part of a convergent alternatively spliced transcript signature across SF3B1 hotspots PMID:22158541
Therapeutic relevance
- Alternatively spliced DLST transcripts may represent a downstream vulnerability in SF3B1-mutant breast cancers, though no direct therapeutic targeting has been reported in the corpus.
Open questions
- Whether DLST splicing dysregulation contributes functionally to the growth defect or metabolic phenotype of SF3B1-mutant cells is unresolved PMID:22158541
Sources
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