a Department of Urology , Daping Hospital/Institute of Surgery Research, Third Military Medical University , Chongqing , China.
b Department of Medical Center , Geneplus-Beijing Institute , Beijing , PR China.
Cancer Biol Ther. 2018 Aug 3;19(8):669-675. doi: 10.1080/15384047.2018.1451278. Epub 2018 Apr 19.
Genetic factors contribute to more than 40% of prostate cancer risk, and mutations in BRCA1 and BRCA2 are well-established risk factors. By using target capture-based deep sequencing to identify potential pathogenic germline mutations, followed by Sanger sequencing to determine the loci of the mutations, we identified a novel pathogenic BRCA2 mutation caused by a cytosine-to-guanine base substitution at position 4211, resulting in protein truncation (p.Ser1404Ter), which was confirmed by immunohistochemistry. Analysis of peripheral blood also identified benign polymorphisms in BRCA2 (c.7397T>C, p.Val2466Ala) and SRD5A2 (c.87G>C, p.Lys29Asn). Analysis of tumor tissues revealed seven somatic mutations in prostate tumor tissue and nine somatic mutations in esophageal squamous carcinoma tissue (single nucleotide polymorphisms, insertions, and deletions). Five-year follow-up results indicate that ADT combined with radiotherapy successfully treated the prostate cancer. To our knowledge, we are the first to report the germline BRCA2 mutation c.4211C>G (p.Ser1404Ter) in prostate cancer. Combined ADT and radiotherapy may be effective in treating other patients with prostate cancer caused by this or similar mutations.
遗传因素导致超过 40%的前列腺癌风险，BRCA1 和 BRCA2 的突变是公认的风险因素。我们使用基于靶向捕获的深度测序来识别潜在的致病性种系突变，然后通过 Sanger 测序来确定突变的位置，鉴定出一种新的致病性 BRCA2 突变，该突变是由第 4211 位胞嘧啶到鸟嘌呤碱基取代引起的，导致蛋白截断（p.Ser1404Ter），免疫组化证实了这一点。对外周血的分析还鉴定出 BRCA2（c.7397T>C，p.Val2466Ala）和 SRD5A2（c.87G>C，p.Lys29Asn）中的良性多态性。对肿瘤组织的分析显示，前列腺肿瘤组织中有七个体细胞突变，食管鳞状细胞癌组织中有九个体细胞突变（单核苷酸多态性、插入和缺失）。五年的随访结果表明，ADT 联合放疗成功治疗了前列腺癌。据我们所知，我们是第一个报道前列腺癌中种系 BRCA2 突变 c.4211C>G（p.Ser1404Ter）的。联合 ADT 和放疗可能对其他由这种或类似突变引起的前列腺癌患者有效。
