【佳学基因检测】通过高灵敏度深度靶向下一代测序进行 KRAS/GNAS 测试改进了内镜超声引导下对疑似胰腺粘液性肿瘤的检查

夫妻备孕基因检测项目要点

体会肿瘤基因解码协会如何提升基因检测的准确性记录《Genes Chromosomes Cancer》在. 2021 Jul;60(7):489-497.发表了一篇题目为《通过高灵敏度深度靶向下一代测序进行 KRAS/GNAS 测试改进了内镜超声引导下对疑似胰腺粘液性肿瘤的检查》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Daniel Schmitz, Daniel Kazdal, Michael Allgäuer, Marcus Trunk, Sylke Vornhusen, Anna-Maria Nahm, Matthias Doll, Simon Weingärtner, Volker Endris, Roland Penzel, Martina Kirchner, Regine Brandt, Olaf Neumann, Holger Sültmann, Jan Budczies, Peter Kienle, Richard Magdeburg, Svetlana Hetjens, Peter Schirmacher, Frank Bergmann, Jochen Rudi, Albrecht Stenzinger, Anna-Lena Volckmar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：

癌胚抗原,细胞学,内镜超声引导下细针抽吸,高通量核苷酸测序,胰腺导管内乳头状粘液性肿瘤

肿瘤靶向治疗基因检测临床应用结果

胰腺囊肿或扩张的胰管通常通过横断面成像发现，但只有粘液性病变可以变成恶性。因此，区分粘液性和非粘液性病变对于适当的患者管理至关重要。基因解码基因检测进行了一项前瞻性研究，包括在诊断内窥镜超声 (EUS) 引导的检查中对无细胞 DNA 进行靶向下一代测序 (NGS)。通过 EUS 引导的 FNA 获得的胰腺囊肿或导管液通过 14 个已知胃肠癌基因（AKT1、BRAF、CTNNB1、EGFR、ERBB2、FBXW7、GNAS、 KRAS、MAP2K1、NRAS、PIK3CA、SMAD4、TP53、APC），检测限低至 0.01% 的变异等位基因频率。基因解码基因检测的研究结果与组织病理学和临床随访相关。筛查了 113 名患有胰腺囊肿和/或胰腺主导管扩张（≥5 mm）的患者。必须排除 66 名患者，主要是由于无法手术或囊肿小（≤10 mm）。招募了 47 名患者进行进一步分析。在 27 例病例中可得到最终诊断，其中包括 8 例阴性对照。在 43/47 (91.5%) 的患者中，NGS 诊断出 KRAS 和/或 GNAS 突变。 27.0% 的 KRAS 突变和 10.0% 的 GNAS 突变病变具有多个突变。 NGS、细胞学和 CEA 检测 KRAS/GNAS 的敏感性和特异性分别为 94.7/100%、38.1/100% 和 42.1/75.0%。 KRAS/GNAS 检测显着优于 CEA (P = .0209) 和细胞学 (P = .0016)。总之，通过深度靶向 NGS 进行的 KRAS/GNAS 检测是区分粘液性和非粘液性胰腺病变的合适基因解码基因检测的研究方法，表明其可用作单一诊断测试。基因解码基因检测的研究结果必须在更大的队列中得到证实。关键词：癌胚抗原；细胞学;内镜超声引导下细针抽吸；高通量核苷酸测序；胰腺导管内乳头状粘液性肿瘤。

肿瘤发生与复发转移国际数据库描述：

Pancreatic cysts or dilated pancreatic ducts are often found by cross-sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non-mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell-free DNA in the diagnostic endoscopic ultrasound (EUS)-guided workup. Pancreatic cyst(s) or main duct fluid obtained by EUS-guided FNA was analysed by carcinoembryonic antigen (CEA), cytology and deep targeted NGS of 14 known gastrointestinal cancer genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) with a limit of detection down to variant allele frequency of 0.01%. Results were correlated to histopathology and clinical follow-up. One hundred and thirteen patients with pancreatic cyst(s) and/or a dilated pancreatic main duct (≥5 mm) were screened. Sixty-six patients had to be excluded, mainly due to inoperability or small cyst size (≤10 mm). Forty-seven patients were enrolled for further analysis. A final diagnosis was available in 27 cases including 8 negative controls. In 43/47 (91.5%) of patients a KRAS- and/or GNAS-mutation was diagnosed by NGS. 27.0% of the KRAS-mutated and 10.0% of the GNAS-mutated lesions harbored multiple mutations. KRAS/GNAS-testing by NGS, cytology, and CEA had a sensitivity and specificity of 94.7/100%, 38.1/100%, and 42.1/75.0%, respectively. KRAS/GNAS-testing was significantly superior to CEA (P = .0209) and cytology (P = .0016). In conclusion, KRAS/GNAS-testing by deep targeted NGS is a suitable method to distinguish mucinous from non-mucinous pancreatic lesions, suggesting its usage as a single diagnostic test. Results must be confirmed in a larger cohort.Keywords: carcinoembryonic antigen; cytology; endoscopic ultrasound-guided fine needle aspiration; high-throughput nucleotide sequencing; intraductal papillary mucinous neoplasms of the pancreas.