【佳学基因检测】晚期前列腺癌的靶向下一代测序确定潜在的治疗靶点和疾病异质性

靶向治疗基因检测医保报销吗—揭密

讨化基因检测机构自我培训教材《肿瘤基因易感位点列表及发生率分析》《Eur Urol》在. 2013 May;63(5):920-6.发表了一篇题目为《晚期前列腺癌的靶向下一代测序确定潜在的治疗靶点和疾病异质性》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Himisha Beltran, Roman Yelensky, Garrett M Frampton, Kyung Park, Sean R Downing, Theresa Y MacDonald, Mirna Jarosz, Doron Lipson, Scott T Tagawa, David M Nanus, Philip J Stephens, Juan Miguel Mosquera, Maureen T Cronin, Mark A Rubin等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

共同装载,联合治疗,高效转染,外泌体,肿瘤靶向

肿瘤靶向治疗基因检测临床应用结果

基因解码基因检测的研究介绍：大多数涉及 DNA 测序的个性化癌症护理策略高度依赖于获得足够的新鲜或冷冻组织。由于转移组织的获取有限，全面评估晚期前列腺癌 (PCa) 的基因组一直具有挑战性。基因解码基因检测的研究目的：证明可与档案福尔马林一起使用的新型下一代测序 (NGS) 平台的可行性- 固定石蜡包埋 (FFPE) 活检组织，以评估晚期 PCa 中所见的 DNA 改变谱。设计、设置和参与者：FFPE 样本（包括档案前列腺切除术和前列腺针活检）来自代表疾病谱的 45 名患者：局部 PCa、转移性激素初治 PCa 和转移性去势抵抗性 PCa (CRPC)。基因解码基因检测还评估了成对的原发灶和转移灶，以了解疾病异质性和疾病进展。干预：从 FFPE 样本中提取至少 50 ng 的肿瘤 DNA，并使用 Illumina HiSeq 2000 平台用于杂交捕获和 NGS。基因解码基因检测的研究结果测量和统计分析：A评估了 182 个癌症相关基因的 3320 个外显子和 14 个常见重排基因的 37 个内含子的基因组改变。基因解码基因检测的研究结果和局限性：基因解码基因检测获得了 >900X 的平均测序深度。总体而言，44% 的 CRPC 存在涉及雄激素受体基因 (AR) 的基因组改变，包括 AR 拷贝数增加（24% 的 CRPC）或 AR 点突变（20% 的 CRPC）。其他经常发生的突变包括跨膜蛋白酶、丝氨酸 2 基因 (TMPRSS2):v-ets erythroblastosis virus E26 癌基因同源物（禽）基因 (ERG) 融合 (44%)；磷酸酶和张力蛋白同源基因（PTEN）丢失（44%）；肿瘤蛋白p53基因（TP53）突变（40%）；视网膜母细胞瘤基因（RB）缺失（28%）； v-myc 骨髓细胞瘤病病毒癌基因同源物（禽）基因（MYC）增益（12%）；和 phosphatidylinositol-4,5-bisphosphate 3-kinase，催化亚基 α 基因 (PIK3CA) 突变 (4%)。涉及对 DNA 修复很重要的关键基因的基因组改变的发生率很高，包括乳腺癌 2、早发基因 (BRCA2) 丢失 (12%) 和共济失调毛细血管扩张症突变基因 (ATM) 突变 (8%)；这些改变可能是聚（二磷酸腺苷 - 核糖）聚合酶抑制剂的靶向。还检测到涉及 v-raf 鼠肉瘤病毒癌基因同源物 B1 基因 (BRAF) 的新颖且可操作的重排。

肿瘤发生与复发转移国际数据库描述：

Background: Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue.Objective: To demonstrate the feasibility of a novel next-generation sequencing (NGS)-based platform that can be used with archival formalin-fixed paraffin-embedded (FFPE) biopsy tissue to evaluate the spectrum of DNA alterations seen in advanced PCa.Design, setting, and participants: FFPE samples (including archival prostatectomies and prostate needle biopsies) were obtained from 45 patients representing the spectrum of disease: localized PCa, metastatic hormone-naive PCa, and metastatic castration-resistant PCa (CRPC). We also assessed paired primaries and metastases to understand disease heterogeneity and disease progression.Intervention: At least 50 ng of tumor DNA was extracted from FFPE samples and used for hybridization capture and NGS using the Illumina HiSeq 2000 platform.Outcome measurements and statistical analysis: A total of 3320 exons of 182 cancer-associated genes and 37 introns of 14 commonly rearranged genes were evaluated for genomic alterations.Results and limitations: We obtained an average sequencing depth of >900X. Overall, 44% of CRPCs harbored genomic alterations involving the androgen receptor gene (AR), including AR copy number gain (24% of CRPCs) or AR point mutation (20% of CRPCs). Other recurrent mutations included transmembrane protease, serine 2 gene (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) gene (ERG) fusion (44%); phosphatase and tensin homolog gene (PTEN) loss (44%); tumor protein p53 gene (TP53) mutation (40%); retinoblastoma gene (RB) loss (28%); v-myc myelocytomatosis viral oncogene homolog (avian) gene (MYC) gain (12%); and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α gene (PIK3CA) mutation (4%). There was a high incidence of genomic alterations involving key genes important for DNA repair, including breast cancer 2, early onset gene (BRCA2) loss (12%) and ataxia telangiectasia mutated gene (ATM) mutations (8%); these alterations are potentially targetable with poly(adenosine diphosphate-ribose)polymerase inhibitors. A novel and actionable rearrangement involving the v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) was also detected.