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Updated: Jul 4, 2026
06:21
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Germline CDK12 variants in aggressive prostate cancer
Sofie H Tolmeijer1, Corinne Maurice-Dror2, Shahneen Sandhu3
1University of British Columbia Vancouver, British Columbia Canada.
Cancer Discovery
|July 2, 2026
Summary
Rare germline CDK12 variants drive lethal metastatic prostate cancer (mPCa). These inherited mutations, found in 0.1% of patients, lead to a specific genomic instability signature and are linked to family cancer histories.
Area of Science:
- Genetics
- Oncology
- Genomic Instability
Background:
- CDK12 mutations are found in 2-7% of metastatic prostate cancer (mPCa) and were previously thought to be exclusively somatic.
- Germline variants are rare genetic alterations inherited from parents.
Purpose of the Study:
- To investigate the role of germline CDK12 truncating variants in metastatic prostate cancer.
- To determine the frequency and clinical significance of germline CDK12 variants in mPCa.
Main Methods:
- Screening of 4,535 metastatic prostate cancer patients for germline CDK12 truncating variants.
- Analysis of tumor genomes for secondary somatic CDK12 variants and genomic instability signatures.
- Comparison of germline variant frequency with large population control cohorts (gnomAD).
- Pedigree analysis to confirm germline variant inheritance.
Main Results:
- Identified five mPCa patients (0.1%) with germline CDK12 truncating variants.
- All patients exhibited CDK12-driven cancers with a distinct genomic instability signature (tandem duplications).
- Germline CDK12 variants were significantly enriched in mPCa compared to controls.
- Family histories and pedigree analyses confirmed inheritance patterns and links to prostate and ovarian cancers.
Conclusions:
- Germline CDK12 truncating variants are a rare but significant driver of lethal metastatic prostate cancer.
- These variants contribute to a specific genomic instability phenotype.
- Germline CDK12 testing may have implications for risk assessment and family cancer counseling.
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