Pan‐Cancer Analysis of CDK12 Loss‐of‐Function Alterations and Their Association with the Focal Tandem‐Duplicator Phenotype

Conclusion.Detection of CDK12‐LOF genomic alterations and their association with FTDs in a diverse spectrum of malignancies suggests that immunotherapy approaches targeting FINAs derived from CDK12‐associated FTDs may be a broadly applicable strategy that could be explored across cancer types in a tumor‐agnostic manner.Implications for Practice.CDK12 inactivation in ovarian and prostate cancer results in the generation of focal tandem duplications, which can cause fusion‐induced neoantigens. In prostate cancer, CDK12 alterations have demonstrated promise as a potential predictive biomarker for response to immune checkpoint blockade. This study evaluated genomic profiling data from>142,000 tumors to determine the prevalence of CDK12 loss‐of‐function genomic alterations across tumor types and demonstrated that CDK12 alterations are associated with the tandem‐duplicator phenotype in cancer types other than ovarian and prostate cancer. The association of CDK12 alterations with focal tandem duplications across broad cancer types suggests that CDK12 inactivation warrants further investigation as a pan‐cancer biomarker for immunotherapy benefit.

Source: The Oncologist - December 9, 2019 Category: Cancer & Oncology Authors: Ethan S. Sokol, Dean Pavlick, Garrett M. Frampton, Jeffrey S. Ross, Vincent A. Miller, Siraj M. Ali, Tamara L. Lotan, Drew M. Pardoll, Jon H. Chung, Emmanuel S. Antonarakis Tags: Cancer Diagnostics and Molecular Pathology Source Type: research