Germline Mutations in Patients With Early-Onset Prostate Cancer

Abstract

ObjectiveTo investigate the inherited mutations and their association with clinical features and treatment response in young-onset prostate cancer patients.MethodTargeted 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.ResultsSixty-two germline mutations in 45 genes were verified in 22 patients. BRCA2 (20.8%) and GJB2 (20.8%) were found to be the most frequently mutated, followed by CHEK2, BRCA1, PALB2, CDKN2A, HOXB13, PPM1D, and RECQL (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.ConclusionMutations 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.

Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma

“…Similarly, we showed that patients with bilateral or multifocal nccRCC are more likely to have pathogenic/likely pathogenic germline mutations. Early-onset cancer is a hallmark of an inherited cancer predisposition (35,36), and studies have shown that patients with mutations in RCC-associated genes, such as VHL, FH, FLCN, and SDHB, are at risk for the development of early-onset RCC (37)(38)(39). Loss of function of MUTYH accounts for 3% of early-onset CRC (40,41).…”

Homologous Recombination Repair Gene Mutations in Prostate Cancer: Prevalence and Clinical Value

“…Targeted sequencing of 139 cancer-related genes in 24 patients under the age of 63 years with PC revealed a total of 62 germline mutations in 45 genes; 22/24 patients harbored germline mutations, and nearly 60% of patients had mutations in DDR genes. BRCA2 (20.8%) and gap junction beta-2 ( GJB2 ) (20.8%) were the most frequently mutated genes [ 44 ]. Mutations in CHEK2 , BRCA1 , PALB2 , cyclin-dependent kinase inhibitor 2A ( CDKN2A ), homeobox protein B13 ( HOXB13 ), protein phosphatase 1D ( PPM1D ), and ATP-dependent DNA helicase Q1 ( RECQL ) were also common (8.3% each) [ 44 ].…”

“…BRCA2 (20.8%) and gap junction beta-2 ( GJB2 ) (20.8%) were the most frequently mutated genes [ 44 ]. Mutations in CHEK2 , BRCA1 , PALB2 , cyclin-dependent kinase inhibitor 2A ( CDKN2A ), homeobox protein B13 ( HOXB13 ), protein phosphatase 1D ( PPM1D ), and ATP-dependent DNA helicase Q1 ( RECQL ) were also common (8.3% each) [ 44 ]. Another targeted sequencing study of 18 DDR genes in 316 patients with PC showed that 9.8% of patients had pathogenic germline mutations in 18 DDR genes [ 45 ].…”

The Expression Characteristics and Function of the RECQ Family in Pan-Cancer

“…Recent studies indicate that RECQs may serve as potential genes responsible for breast cancer susceptibility, with missense mutations in these genes playing a role in the development of familial breast cancer [ 15 , 16 , 17 ]. In addition, RECQs are linked to thyroid carcinoma, prostate cancer, and ovarian cancer [ 18 , 19 ]. RECQs play a wide-ranging and varied role in the regulation of cancer and are closely associated with renowned molecules or pathways that control cancer, thereby having significant implications for cancer treatment [ 20 ].…”