2026-07-09 ブリティッシュコロンビア大学（UBC）
＜関連情報＞
- https://news.ubc.ca/2026/07/researchers-discover-new-form-of-hereditary-prostate-cancer/
- https://aacrjournals.org/cancerdiscovery/article-abstract/doi/10.1158/2159-8290.CD-26-0084/786384/Germline-CDK12-variants-in-aggressive-prostate
悪性前立腺癌における生殖細胞系CDK12変異 Germline CDK12 variants in aggressive prostate cancer
Sofie H. Tolmeijer;Corinne Maurice-Dror;Shahneen Sandhu;Claire M. de la Calle;Christian Kollmannsberger;Mohamed Adil;Catherine K. Wang;Andrew J. Murtha;Gráinne Donnellan;Nielka P. van Erp;Niven Mehra;Michael S. Hofman;Arun A. Azad;Ian D. Davis;Andries M. Bergman;Wilbert Zwart;Kim van der Zande;Lesley Seymour;Peter C. Black;Vahid Akbari;Lilian Cordova;Peter M. Lansdorp;Steven JM. Jones;Peter S. Nelson;Elena Castro;Kasmintan A. Schrader;Gavin Ha;Heather H. Cheng;Piet Ost;David Olmos;Kim N. Chi;Colin C. Pritchard;Alexander W. Wyatt
Cancer Discovery Published:July 02 2026
DOI:https://doi.org/10.1158/2159-8290.CD-26-0084
Abstract
CDK12 mutations occur in 2-7% of metastatic prostate cancers (mPCa) and are considered to be exclusively somatic. Here, we identified five patients with mPCa (ages 44-62) harboring germline CDK12 truncating variants among 4,535 tested (0.1%). All had CDK12-driven cancers defined by an additional somatic CDK12 variant and the CDK12-specific hallmark genomic instability signature characterized by hundreds of tandem duplications. Two patients had multiple independent CDK12-driven tumors with distinct secondary somatic CDK12 variants. Germline CDK12 truncating variants were enriched in mPCa compared to gnomAD V4.1.0 controls (n=807,162; odds ratio 11.4, 95% CI 3.6-27.8) and V2.1.1 non-cancer controls (n=134,187; odds ratio 29.6; 95% CI 6.8-28.6). Family history revealed multiple related individuals with prostate or ovarian cancer, and germline variant inheritance was confirmed in the two tested pedigrees. Our data suggest that germline CDK12 truncating variants are a rare driver of lethal mPCa.
