AUTHOR=Tang Tang , Tan Xintao , Wang Ze , Wang Shuo , Wang Yapeng , Xu Jing , Wei Xiajie , Zhang Dianzheng , Liu Qiuli , Jiang Jun 

TITLE=Germline Mutations in Patients With Early-Onset Prostate Cancer

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.826778

DOI=10.3389/fonc.2022.826778

ISSN=2234-943X

ABSTRACT=<sec><title>Objective</title><p>To investigate the inherited mutations and their association with clinical features and treatment response in young-onset prostate cancer patients.</p></sec><sec><title>Method</title><p>Targeted gene sequencing on 139 tumor susceptibility genes was conducted with a total of 24 patients diagnosed with PCa under the age of 63 years old. Meanwhile, the related clinical information of those patients is collected and analyzed.</p></sec><sec><title>Results</title><p>Sixty-two germline mutations in 45 genes were verified in 22 patients. <italic>BRCA2</italic> (20.8%) and <italic>GJB2</italic> (20.8%) were found to be the most frequently mutated, followed by <italic>CHEK2, BRCA1, PALB2, CDKN2A, HOXB13, PPM1D</italic>, and <italic>RECQL</italic> (8.3% of each, 2/24). Of note, 58.3% (14/24) patients carry germline mutations in DNA repair genes (DRGs). Four families with HRR (homologous recombination repair)-related gene mutations were described and analyzed in detail. Two patients with BRCA2 mutation responded well to the combined treatment of androgen deprivation therapy (ADT) and radiotherapy/chemotherapy.</p></sec><sec><title>Conclusion</title><p>Mutations in DRGs are more prevalent in early-onset PCa with advanced clinical stages, and these patients had shorter progression-free survival. ADT Combined with either radiotherapy or chemotherapy may be effective in treating PCa caused by HRR-related gene mutations.</p></sec>