Faias Sandra, Duarte Marlene, Pereira Luísa, Chaves Paula, Cravo Marília, Dias Pereira Antonio, Albuquerque Cristina
Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE, Lisboa 1099-023, Portugal.
Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE, Lisboa 1099-023, Portugal.
World J Gastrointest Oncol. 2020 Sep 15;12(9):1056-1064. doi: 10.4251/wjgo.v12.i9.1056.
Guanine nucleotide-binding protein, alpha stimulating () mutations are characteristic of intraductal papillary mucinous neoplasms (IPMNs). Pancreatic ductal adenocarcinomas (PDACs) harboring mutations originate in IPMNs. is a complex imprinted locus that produces five transcripts regulated by differential methylated regions, , , , , and .
To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts.
locus methylation was analyzed in archival pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific-multiplex ligation dependent probe amplification. Results were normalized and analyzed using Coffalyser.Net software.
Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for and mutations were studied. The final diagnoses were surgical (11) and clinicopathological (41), including 30 benign cysts, 14 pre-malignant cyst, and eight malignant cysts. Methylation changes at , and especially were more frequent in malignant cysts, and and were useful for diagnosis. A combined variable defined as " locus methylation changes" was significantly associated with malignancy (6/8 malignant cysts and only 2/20 benign cysts) and improved classification. Hypermethylation in both maternally () and paternally () derived promoters was found in 3/3 PDACs.
This is the first study to identify methylation changes in the locus, improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.
鸟嘌呤核苷酸结合蛋白α刺激（）突变是导管内乳头状黏液性肿瘤（IPMNs）的特征。携带 突变的胰腺导管腺癌（PDACs）起源于IPMNs。 是一个复杂的印记基因座，产生由差异甲基化区域、、、、和调控的五种转录本。
评估GNAS基因座差异甲基化区域的甲基化变化是否有助于胰腺囊肿的恶性进展。
通过甲基化特异性多重连接依赖探针扩增法，对经内镜超声引导细针穿刺获取的存档胰腺囊肿液（PCF）中的基因座甲基化进行分析。使用Coffalyser.Net软件对结果进行标准化和分析。
研究了52份经内镜超声引导细针穿刺获取的PCF样本，这些样本先前已对 和 突变进行了特征分析。最终诊断为手术诊断（11例）和临床病理诊断（41例），包括30例良性囊肿、14例癌前囊肿和8例恶性囊肿。在恶性囊肿中，、尤其是 的甲基化变化更为频繁， 和 有助于诊断。定义为“基因座甲基化变化”的联合变量与恶性肿瘤显著相关（8例恶性囊肿中有6例，而20例良性囊肿中仅2例），并改善了分类。在3/3的PDACs中发现母源（）和父源（）启动子均存在高甲基化。
这是第一项鉴定基因座甲基化变化的研究，改善了恶性胰腺囊肿的诊断，并提示其在进展为PDAC中的作用。
