Degron Disruption in Small Cell Lung Cancer

Abstract

Degron disruption is an underappreciated mechanism of oncogenicity in cancer and may have a prognostic role in small cell lung cancer. A degron is a short sequence of peptides within a protein that is recognized by E3 ubiquitin ligases. In cancer, degrons are often disrupted due to somatic mutations There are well known degron disrupting mutations in oncoproteins, such as CTNNB1, NFE2L2, and MET that recur among multiple cancer types. It is estimated that degron disrupting mutations occur in 10 percent of cancers and that over 19 percent of cancer driver gene mutations affect the ubiquitin-proteasome system. These analyses did not include SCLC as this tumor type is not part of TCGA. Given that degron disruption frequently occurs in cancer driver genes across tumor types, degrons frequently are not commonly annotated in genomic datasets, and degron disruption may result in therapeutic vulnerabilities, we hypothesized that subsets of small cell lung cancer might share common degron disruption events which could elucidate tumor biology and potentially identify novel treatments.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2023
Accession Number
AD1212983

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  • Aaron Mansfield

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  • Mayo Clinic

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