2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.121 Kim Lauer NACLC23 Abstract

PP01.121 Kim Lauer NACLC23 Abstract

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Researchers have developed a bioinformatics workflow to identify disruptions in degrons, which are short sequences within proteins recognized by E3 ubiquitin ligases and involved in the degradation of proteins through the ubiquitin-proteasome system. Degron disruptions have been associated with cancer. The study focused on small cell lung cancer (SCLC) and analyzed somatic mutations, gene fusions, and aberrant RNA splicings to detect disruptions in internal and terminal degrons. The researchers used a tool called DeepDegron1 to predict terminal degrons and utilized previously reported degrons to define internal degrons. They also developed novel algorithms to predict and assemble RNA transcripts resulting from fusion events and splicing events. The analysis identified recurrent degron disruptions in the FLG gene and identified non-recurrent disruptions in several known oncogenes including KRAS, DOT1L, EPHA7, and MITF, among others. In addition, gene fusions and RNA splicings were found to interrupt degrons in known oncogenes. The study highlights the importance of identifying degron disruptions as they can contribute to our understanding of disease progression and help identify potential drug targets. Further research is needed to validate and determine the biological and clinical relevance of these degron disruptions in SCLC.

Keywords

bioinformatics workflow

degrons

E3 ubiquitin ligases

ubiquitin-proteasome system

cancer

small cell lung cancer

somatic mutations

gene fusions

aberrant RNA splicings

FLG gene