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Methylation changes at the GNAS imprinted locus in pancreatic cystic neoplasms are important for the diagnosis of malignant cysts

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World Journal of Gastrointestinal Oncology 2020年第9期12卷 1056-1064页

作者： Sandra Faias Marlene Duarte Luísa Pereira Paula Chaves Marília Cravo Antonio Dias Pereira Cristina Albuquerque Department of Gastroenterology Instituto Português de Oncologia de Lisboa Francisco GentilEPELisboa 1099-023Portugal Faculty of Health Sciences University of Beira InteriorCovilhã6200-506Portugal Unidade de Investigação em Patobiologia Molecular(UIPM) Instituto Português de Oncologia de Lisboa Francisco GentilEPELisboa 1099-023Portugal Centro de Matemática e Aplicações(CMA-UBI) Universidade da Beira InteriorCovilhã6200-506Portugal Department of Pathology Instituto Português de Oncologia de Lisboa Francisco GentilEPELisboa 1099-023Portugal Department of Gastroenterology Hospital BeatrizÂngeloLoures 2674-514Portugal

BACKGROUND Guanine nucleotide-binding protein,alpha stimulating(GNAS)mutations are characteristic of intraductal papillary mucinous neoplasms(IPMNs).Pancreatic ductal adenocarcinomas(PDACs)harboring GNAS mutations originate in *** is a complex imprinted locus that produces five transcripts regulated by differential methylated regions,NESP55,GNASAS,GNASXL,GNAS1A,and *** To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic *** GNAS 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 *** were normalized and analyzed using *** *** Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were *** final diagnoses were surgical(11)and clinicopathological(41),including 30 benign cysts,14 pre-malignant cyst,and eight malignant *** changes at NESP55,GNASAS,GNAS1A,and especially GNASXL were more frequent in malignant cysts,and NESP55 and GNASAS were useful for diagnosis.A combined variable defined as“GNAS locus methylation changes”was significantly associated with malignancy(6/8 malignant cysts and only 2/20 benign cysts)and improved *** in both maternally(NESP55)and paternally(GNASXL)derived promoters was found in 3/3 *** This is the first study to identify methylation changes in the GNAS locus,improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.

关键词： Intraductal papillary mucinous neoplasms pancreas cyst Methylation Biomarker GNAS locus Pancreatic neoplasm

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