【佳學(xué)基因檢測】胰腺囊液細(xì)胞和液體部分的下一代測序支持區(qū)分 IPMN 和假性囊腫，并揭示具有多個(gè)突變驅(qū)動(dòng)克隆的病例：前瞻性 ZYSTEUS 生物標(biāo)志物研究的初步發(fā)現(xiàn)

腫瘤基因療法說明

開會(huì)學(xué)習(xí)腫瘤的基因組學(xué)特征與治療方案設(shè)計(jì)《腫瘤基因突變度與預(yù)防策略的實(shí)施計(jì)劃》《Genes Chromosomes Cancer》在. 2019 Jan;58(1):3-11.發(fā)表了一篇題目為《胰腺囊液細(xì)胞和液體部分的下一代測序支持區(qū)分 IPMN 和假性囊腫，并揭示具有多個(gè)突變驅(qū)動(dòng)克隆的病例：前瞻性 ZYSTEUS 生物標(biāo)志物研究的初步發(fā)現(xiàn)》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由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。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤找到治療藥物的機(jī)構(gòu)臨床研究內(nèi)容關(guān)鍵詞：

EUS 引導(dǎo)的 FNA,液體活檢,粘液性胰腺囊腫,下一代測序,胰腺囊腫液

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

大約一半的胰腺囊腫是腫瘤性的，主要包括導(dǎo)管內(nèi)乳頭狀粘液性腫瘤 (IPMN)，可進(jìn)展為浸潤性癌。目前的福岡指南在預(yù)測無癥狀胰腺囊腫進(jìn)展方面的敏感性和特異性有限。我們提出了前瞻性 ZYSTEUS 生物標(biāo)志物研究的初步結(jié)果，調(diào)查 (i) 通過液體活檢檢測 IPMN 中的驅(qū)動(dòng)突變在技術(shù)上是否可行，(ii) IPMN 的哪個(gè)隔室賊適合分析，以及 (iii) 對(duì)臨床診斷的影響。 22 名符合臨床納入標(biāo)準(zhǔn)的患者被納入 ZYSTEUS。 15 例患者接受了超聲內(nèi)鏡 (EUS) 引導(dǎo)下的細(xì)針抽吸和細(xì)胞學(xué)診斷。分離每個(gè)病例的囊腫的細(xì)胞和液體部分，并進(jìn)行深度靶向下一代測序（NGS）。連續(xù)收集臨床參數(shù)、影像學(xué)檢查結(jié)果（EUS 和 MRI）和隨訪數(shù)據(jù)。所有 IPMN 病例 (n = 12) 在 KRAS (n = 11) 或 GNAS (n = 4) 中都顯示出至少一個(gè)突變。三個(gè)病例同時(shí)顯示 KRAS 和 GNAS 突變。 6 例攜帶多個(gè) KRAS/GNAS 突變。在三例假性囊腫病例中，未檢測到 KRAS 或 GNAS 突變。 DNA 產(chǎn)量更高，并且在細(xì)胞部分中表現(xiàn)出更高的突變多樣性。總之，胰腺囊液中的突變檢測在技術(shù)上是可行的，在細(xì)胞中的結(jié)果比在液體部分中的結(jié)果更高效。目前的結(jié)果表明，與成像一起，靶向測序支持區(qū)分 IPMN 和假性囊腫。 ZYSTEUS 的前瞻性設(shè)計(jì)將有助于深入了解 NGS 在術(shù)前風(fēng)險(xiǎn)分層中的診斷價(jià)值。我們的數(shù)據(jù)為 IPMN 的寡克隆性質(zhì)提供了證據(jù)。關(guān)鍵詞：EUS 引導(dǎo)的 FNA；液體活檢；粘液性胰腺囊腫；下一代測序；胰腺囊腫液。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

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.