CDK12 inactivation across solid tumors: an actionable genetic subtype

Catherine H. Marshall MD MPH1,*, Eddie L. Imada MS2,*, Zhuojun Tang MS3, Luigi Marchionni MD PhD3, Emmanuel S. Antonarakis MD1

1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

2Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

3Sidney Kimmel Comprehensive Cancer Center and Center for Computational Genomics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Correspondence to:

Emmanuel S. Antonarakis, email:eantona1@jhmi.edu

Keywords: prostate cancer; CDK12; genetics; immunotherapy; biomarkers

Received: February 11, 2019 Accepted: April 6, 2019 Published: May 10, 2019


Inactivating CDK12 alterations have been reported in ovarian and prostate cancers and may have therapeutic implications; however, the prevalence of these mutations across other cancer types is unknown. We searched the cBioPortal and GENIE Project (public release v4.1) databases for cancer types with > 200 sequenced cases, that included patients with metastatic disease, and in which the occurrence of at least monoallelic CDK12 alterations was > 1%. The prevalence of at least monoallelic CDK12 mutations was highest in bladder cancer (3.7%); followed by prostate (3.4%), esophago-gastric (2.1%) and uterine cancers (2.1%). Biallelic CDK12 inactivation was highest in prostate cancer (1.8%), followed by ovarian (1.0%) and bladder cancers (0.5%). These results are the first (to our knowledge) to estimate the prevalence of monoallelic and biallelic CDK12 mutations across multiple cancer types encompassing over 15,000 cases.

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