UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results
Objective Germline BRCA2 pathogenic variants (PVs) are known to cause ~4% of prostate cancer, but other homologous repair genes, BRCA1, ATM, PALB2 and Lynch syndrome genes are also involved. Our objective was to assess the contribution of germline and somatic gene variants to prostate cancer.Methods...
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BMJ Publishing Group
2025-02-01
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| Series: | BMJ Oncology |
| Online Access: | https://bmjoncology.bmj.com/content/4/1/e000592.full |
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| author | Helene Schlecht Emma R Woodward D Gareth Evans Fiona Lalloo George Burghel Ashwin Sachdeva Andrew Hudson Robert Bristow Omi Parikh |
| author_facet | Helene Schlecht Emma R Woodward D Gareth Evans Fiona Lalloo George Burghel Ashwin Sachdeva Andrew Hudson Robert Bristow Omi Parikh |
| author_sort | Helene Schlecht |
| collection | DOAJ |
| description | Objective Germline BRCA2 pathogenic variants (PVs) are known to cause ~4% of prostate cancer, but other homologous repair genes, BRCA1, ATM, PALB2 and Lynch syndrome genes are also involved. Our objective was to assess the contribution of germline and somatic gene variants to prostate cancer.Methods and analysis We reviewed germline/tumour DNA testing from 450 localised or metastatic prostate cancer cases in NW England mainly from 2022 to 2024. ORs for additional genes used detection rates in controls from the BRIDGES study.Results 450 cases underwent BRCA1/2 germline/somatic testing with 2 germline PVs in BRCA1 (0.4%) and 27 in BRCA2 (6.0%)—total 6.4% and 6/328 (1.8%) in ATM. There were 280 metastatic prostate cancer samples tested with 11 (4%) somatic BRCA2 and 7 (2.7%) somatic ATM identified with 1 somatic BRCA1. Total PVs in BRCA2 were 31/280 (11%), including germline and indeterminate. CDK12 somatic PVs were found in 9/220 (4.1%), including 2 digenic with BRCA2 and 2 which were biallelic.Conclusion In this continuous clinical evaluation, BRCA2 is the most frequently identified prostate cancer gene with over 10% involvement in metastatic disease. BRCA2 and CDK12 somatic PVs do not appear to be mutually exclusive. BRCA1 does not appear to be a significant contributor to prostate cancer progression. |
| format | Article |
| id | doaj-art-afe6872f5d874ddd925df47f372c4709 |
| institution | OA Journals |
| issn | 2752-7948 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Oncology |
| spelling | doaj-art-afe6872f5d874ddd925df47f372c47092025-08-20T02:15:38ZengBMJ Publishing GroupBMJ Oncology2752-79482025-02-014110.1136/bmjonc-2024-000592UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first resultsHelene Schlecht0Emma R Woodward1D Gareth Evans2Fiona Lalloo3George Burghel4Ashwin Sachdeva5Andrew Hudson6Robert Bristow7Omi Parikh85 North West Genomic Laboratory Hub, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UKDivision of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK4 Manchester Centre for Genomic Medicine, St Mary’s Hospital, Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK4 Genomic Medicine, North West Genomic Medicine Service Alliance, Manchester, UK1 Genomic Medicine, Manchester Academic Health Science Centre, Manchester, UKDepartment of Surgery, The Christie Hospital NHS Trust, Manchester, UK3Texas Tech University Health Sciences CenterDivision of Gynecologic Oncology, University of California Irvine, Orange, California, USA3 Clinical Oncology, Royal Preston Hospital, Preston, UKObjective Germline BRCA2 pathogenic variants (PVs) are known to cause ~4% of prostate cancer, but other homologous repair genes, BRCA1, ATM, PALB2 and Lynch syndrome genes are also involved. Our objective was to assess the contribution of germline and somatic gene variants to prostate cancer.Methods and analysis We reviewed germline/tumour DNA testing from 450 localised or metastatic prostate cancer cases in NW England mainly from 2022 to 2024. ORs for additional genes used detection rates in controls from the BRIDGES study.Results 450 cases underwent BRCA1/2 germline/somatic testing with 2 germline PVs in BRCA1 (0.4%) and 27 in BRCA2 (6.0%)—total 6.4% and 6/328 (1.8%) in ATM. There were 280 metastatic prostate cancer samples tested with 11 (4%) somatic BRCA2 and 7 (2.7%) somatic ATM identified with 1 somatic BRCA1. Total PVs in BRCA2 were 31/280 (11%), including germline and indeterminate. CDK12 somatic PVs were found in 9/220 (4.1%), including 2 digenic with BRCA2 and 2 which were biallelic.Conclusion In this continuous clinical evaluation, BRCA2 is the most frequently identified prostate cancer gene with over 10% involvement in metastatic disease. BRCA2 and CDK12 somatic PVs do not appear to be mutually exclusive. BRCA1 does not appear to be a significant contributor to prostate cancer progression.https://bmjoncology.bmj.com/content/4/1/e000592.full |
| spellingShingle | Helene Schlecht Emma R Woodward D Gareth Evans Fiona Lalloo George Burghel Ashwin Sachdeva Andrew Hudson Robert Bristow Omi Parikh UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results BMJ Oncology |
| title | UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results |
| title_full | UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results |
| title_fullStr | UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results |
| title_full_unstemmed | UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results |
| title_short | UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results |
| title_sort | uk based clinical testing programme for somatic and germline brca1 2 atm and cdk12 mutations in prostate cancer first results |
| url | https://bmjoncology.bmj.com/content/4/1/e000592.full |
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