Details

Autor(en) / Beteiligte

• Wu, Junlong
• Wei, Yu
• Pan, Jian
• Jin, Shengming
• Gu, Weijie
• Gan, Hualei
• Zhu, Yao
• Ye, Ding‐Wei

Titel

Prevalence of comprehensive DNA damage repair gene germline mutations in Chinese prostate cancer patients

Ist Teil von

• International journal of cancer, 2021-02, Vol.148 (3), p.673-681

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Germline DNA damage repair (DDR) deficiency has been associated with increased cancer risk, poor prognosis and therapeutic opportunity for prostate cancer (PCa) patients. However, the landscape of germline mutations in PCa covering comprehensive DDR genes has not been reported. We performed whole‐exome sequencing in 246 patients who meet the National Cancer Center Network guidelines for genetic testing and analyzed variants in 276 DDR genes, which was from the Cancer Genome Atlas. A total of 79 deleterious germline alterations in 60 DDR genes were identified in 31% (76/246) patients. Mutations were found in nine DDR pathways, including 11.8% men in homologous recombination repair (HR) pathways, 2.4% men in mismatch repair (MMR) pathway and 16.7% (41/246) patients in non‐HR/MMR pathways. In HRR and MMR pathways, mutations were mostly identified in BRCA2 (5.3%), HFM1 (0.8%), ZSWIM7 (0.8%), MSH2 (0.8%) and MSH3 (0.8%). When compared with the cancer‐free cohort, POLN and POLG conferred high risk to PCa with odds ratio 6.9 and 20.5, respectively. We provided a comprehensive view of germline DDR gene mutations in PCa patients. We also identified two potential PCa predisposition genes: POLN and POLG, which have not been reported in the Western population, confirming the necessity of customizing a multigene panel for Chinese PCa patients. What's new? Germline DNA damage repair (DDR) deficiency is associated with increased cancer risk and poor prognosis inprostate cancer. However, a comprehensive view of DNA DDR germline gene mutations has not been reported. Through sequencing germline DNA from 246 Chinese prostate cancer patients, here the authors identified 79 pathogenic variants in 60 genes involved in nine DNA repair pathways. Almost a third of patients carried germline pathogenic DDR gene mutations—40% of them in homologous recombination or mismatch repair genes and 60%in other DNA repair pathways. The findings indicate the potential benefit of developing new drugs targeting other DDR pathways.