PDF(Sci-hub)
Abstract：
UNASSIGNED: Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions.
UNASSIGNED: Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband\'s peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband\'s family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.
UNASSIGNED: Two previously unreported germline mutations in the DDR pathway, BRCA2 (c.8474_8487delCATACCCTATACAG, p.A2825Vfs*15) and PALB2 (c.472delC, p.Q158Rfs*19) were identified in a patient with metastatic PCa. A specific therapeutic regimen including androgen deprivation therapy, locally radical radiotherapy, and systemic platinum chemotherapy worked well against his cancer. In addition, the metastatic ovarian cancer in the proband\'s half-sister harboring the same BRCA2 germline mutation also responded well to platinum chemotherapy.
UNASSIGNED: The newly identified germline mutations in DDR plays important role in PCa development. Since specific regimen worked well against this cancer, screening of DDR mutation could provide better management for patients with these mutation-mediated PCa.
UNASSIGNED: Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband\'s peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband\'s family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.
UNASSIGNED: Two previously unreported germline mutations in the DDR pathway, BRCA2 (c.8474_8487delCATACCCTATACAG, p.A2825Vfs*15) and PALB2 (c.472delC, p.Q158Rfs*19) were identified in a patient with metastatic PCa. A specific therapeutic regimen including androgen deprivation therapy, locally radical radiotherapy, and systemic platinum chemotherapy worked well against his cancer. In addition, the metastatic ovarian cancer in the proband\'s half-sister harboring the same BRCA2 germline mutation also responded well to platinum chemotherapy.
UNASSIGNED: The newly identified germline mutations in DDR plays important role in PCa development. Since specific regimen worked well against this cancer, screening of DDR mutation could provide better management for patients with these mutation-mediated PCa.
摘要：
■与DNA损伤反应（DDR）有关的突变引起的功能丧失是约20％前列腺癌（PCa）的发展和进展的原因。一些突变可用于癌症风险评估和明智的治疗决策。
■用从先证者的外周血中纯化的总DNA对11个基因进行基于目标捕获的深度测序。进行Sanger测序以筛选先证者家族成员中潜在的种系突变。用从肿瘤组织纯化的DNA进行一组1,021个基因的靶向测序。
■DDR途径中两个以前未报告的种系突变，BRCA2（c.8474_8487delCATACCCTATACAG，p.A2825Vfs*15）和PALB2（c.472delC，p.Q158Rfs*19）在转移性PCa患者中鉴定。一个具体的治疗方案，包括雄激素剥夺治疗，局部根治性放疗，全身铂化疗对他的癌症效果很好。此外,在先证者的同父异母姐妹中，携带相同BRCA2种系突变的转移性卵巢癌也对铂类化疗反应良好。
■新发现的DDR种系突变在PCa发育中起重要作用。因为特定的治疗方案对这种癌症效果很好，DDR突变的筛查可以为这些突变介导的PCa患者提供更好的治疗。
■用从先证者的外周血中纯化的总DNA对11个基因进行基于目标捕获的深度测序。进行Sanger测序以筛选先证者家族成员中潜在的种系突变。用从肿瘤组织纯化的DNA进行一组1,021个基因的靶向测序。
■DDR途径中两个以前未报告的种系突变，BRCA2（c.8474_8487delCATACCCTATACAG，p.A2825Vfs*15）和PALB2（c.472delC，p.Q158Rfs*19）在转移性PCa患者中鉴定。一个具体的治疗方案，包括雄激素剥夺治疗，局部根治性放疗，全身铂化疗对他的癌症效果很好。此外,在先证者的同父异母姐妹中，携带相同BRCA2种系突变的转移性卵巢癌也对铂类化疗反应良好。
■新发现的DDR种系突变在PCa发育中起重要作用。因为特定的治疗方案对这种癌症效果很好，DDR突变的筛查可以为这些突变介导的PCa患者提供更好的治疗。
