Fusion-associated neoantigen burden and predicted immunogenicity of CDK12 biallelic loss-of-function tumors vary substantially across cancer types


Andrew Elliott, Phillip Stafford, Jian Zhang, Qing Zhang, Jeff Swensen, Daniel Martin, Joanne Xiu, Zoran Gatalica, Daniel Vaena, Elisabeth Heath, W. Michael Korn

Fusion rates and predicted neoantigen load varied significantly between CDK12
biallelic LOF tumors across cancer types, highlighting the value of biomarkers with a
quantitative, phenotypic and/or immunogenic readout.
• Co-occurrence of dMMR/MSI-High with CDK12 biallelic LOF correlated with a lower
fusion rate and recurrent CDK12 frameshift mutations at poly-nucleotide tracts,
suggesting CDK12 mutations are a secondary effect in these tumors.
• We propose that fusion rates are linked to CDK12 alterations and may serve as useful
biomarker to enhance our ability to identify responders of ICI therapy.

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