【佳学基因检测】胰腺囊液细胞和液体部分的下一代测序支持区分 IPMN 和假性囊肿，并揭示具有多个突变驱动克隆的病例：前瞻性 ZYSTEUS 生物标志物研究的初步发现

肿瘤基因疗法说明

开会学习肿瘤的基因组学特征与治疗方案设计《肿瘤基因突变度与预防策略的实施计划》《Genes Chromosomes Cancer》在. 2019 Jan;58(1):3-11.发表了一篇题目为《胰腺囊液细胞和液体部分的下一代测序支持区分 IPMN 和假性囊肿，并揭示具有多个突变驱动克隆的病例：前瞻性 ZYSTEUS 生物标志物研究的初步发现》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Anna-Lena Volckmar , Volker Endris , Matthias M Gaida , Jonas Leichsenring , Fabian Stögbauer , Michael Allgäuer , Moritz von Winterfeld , Roland Penzel , Martina Kirchner , Regine Brandt , Olaf Neumann , Holger Sültmann , Peter Schirmacher , Jochen Rudi , Daniel Schmitz , Albrecht Stenzinger  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。

肿瘤找到治疗药物的机构临床研究内容关键词：

EUS 引导的 FNA,液体活检,粘液性胰腺囊肿,下一代测序,胰腺囊肿液

肿瘤靶向治疗基因检测临床应用结果

大约一半的胰腺囊肿是肿瘤性的，主要包括导管内乳头状粘液性肿瘤 (IPMN)，可进展为浸润性癌。目前的福冈指南在预测无症状胰腺囊肿进展方面的敏感性和特异性有限。我们提出了前瞻性 ZYSTEUS 生物标志物研究的初步结果，调查 (i) 通过液体活检检测 IPMN 中的驱动突变在技术上是否可行，(ii) IPMN 的哪个隔室最适合分析，以及 (iii) 对临床诊断的影响。 22 名符合临床纳入标准的患者被纳入 ZYSTEUS。 15 例患者接受了超声内镜 (EUS) 引导下的细针抽吸和细胞学诊断。分离每个病例的囊肿的细胞和液体部分，并进行深度靶向下一代测序（NGS）。连续收集临床参数、影像学检查结果（EUS 和 MRI）和随访数据。所有 IPMN 病例 (n = 12) 在 KRAS (n = 11) 或 GNAS (n = 4) 中都显示出至少一个突变。三个病例同时显示 KRAS 和 GNAS 突变。 6 例携带多个 KRAS/GNAS 突变。在三例假性囊肿病例中，未检测到 KRAS 或 GNAS 突变。 DNA 产量更高，并且在细胞部分中表现出更高的突变多样性。总之，胰腺囊液中的突变检测在技术上是可行的，在细胞中的结果比在液体部分中的结果更可靠。目前的结果表明，与成像一起，靶向测序支持区分 IPMN 和假性囊肿。 ZYSTEUS 的前瞻性设计将有助于深入了解 NGS 在术前风险分层中的诊断价值。我们的数据为 IPMN 的寡克隆性质提供了证据。关键词：EUS 引导的 FNA；液体活检；粘液性胰腺囊肿；下一代测序；胰腺囊肿液。

肿瘤发生与复发转移国际数据库描述：

Approximately half of all pancreatic cysts are neoplastic, mainly comprising intraductal papillary mucinous neoplasms (IPMN), which can progress to invasive carcinoma. Current Fukuoka guidelines have limited sensitivity and specificity in predicting progression of asymptomatic pancreatic cysts. We present first results of the prospective ZYSTEUS biomarker study investigating (i) whether detection of driver mutations in IPMN by liquid biopsy is technically feasible, (ii) which compartment of IPMN is most suitable for analysis, and (iii) implications for clinical diagnostics. Twenty-two patients with clinical inclusion criteria were enrolled in ZYSTEUS. Fifteen cases underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration and cytological diagnostics. Cellular and liquid fraction of the cysts of each case were separated and subjected to deep targeted next generation sequencing (NGS). Clinical parameters, imaging findings (EUS and MRI), and follow-up data were collected continuously. All IPMN cases (n = 12) showed at least one mutation in either KRAS (n = 11) or GNAS (n = 4). Three cases showed both KRAS and GNAS mutations. Six cases harbored multiple KRAS/GNAS mutations. In the three cases with pseudocysts, no KRAS or GNAS mutations were detected. DNA yields were higher and showed higher mutation diversity in the cellular fraction. In conclusion, mutation detection in pancreatic cyst fluid is technically feasible with more robust results in the cellular than in the liquid fraction. Current results suggest that, together with imaging, targeted sequencing supports discrimination of IPMN from pseudocysts. The prospective design of ZYSTEUS will provide insight into diagnostic value of NGS in preoperative risk stratification. Our data provide evidence for an oligoclonal nature of IPMN.Keywords: EUS-guided FNA; liquid biopsy; mucinous pancreatic cyst; next generation sequencing; pancreatic cyst fluid.