GNAS mutation detection in circulating cell-free DNA is a specific predictor for intraductal papillary mucinous neoplasms of the pancreas, especially for intestinal subtype

Abstract

Pancreatic cystic neoplasms (PCNs) are a heterogeneous group with varying risks of malignancy. To explore the clinical utility of liquid biopsy in cyst type classification, we analyzed the GNAS/KRAS mutations in circulating cell-free DNA (cfDNA) obtained from 57 patients with histologically diagnosed PCNs, including 34 with intraductal papillary mucinous neoplasms (IPMNs) and compared the mutant allele prevalence and variant patterns with the paired resected specimens using next-generation sequencing. The positive prevalence of GNAS mutations in cfDNA of patients with IPMN (n = 11, 32%) was significantly higher than that in those with other PCNs (0%, P = 0.002). Conversely, KRAS mutations were detected in cfDNA of only 2 (6%) IPMN patients. The paired-sample comparison revealed highly concordance between the GNAS mutation status of cfDNA and resected IPMN specimens. Similar distributions of GNAS mutation positivity in cfDNA were observed across the different histological grades, whereas IPMNs with intestinal subtype showed a significantly higher prevalence of GNAS mutations than other subtypes (P = 0.030). GNAS mutation positivity in cfDNA was significantly associated with the acellular mucin pool of histological findings in primary IPMN lesions (P = 0.017). Detection of GNAS mutation in cfDNA can serve as a novel biomarker for cyst type classification and differentiation of intestinal subtype IPMN from the other PCNs.

A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation

“…Pancreatic IPMNs specifically have GNAS mutation at exon 8 (Arg201Cys or Arg201His) among pancreatic neoplasms [ 5 , 6 ]. Approximately half of pancreatic IPMNs have GNAS mutation but none of pancreatic duct adenocarcinomas have such a mutation [ 5 ].…”

“…Pancreatic neoplasms such as pancreatic duct adenocarcinomas, IPMNs and solid pseudopapillary neoplasms might have gene mutations of K-ras , GNAS , p16 , TP53 , CTNNB1 , etc [ 5 , 6 ]. Among these mutations, K-ras mutation could be found in both pancreatic duct adenocarcinomas and IPMNs, but GNAS mutation at exon 8 (Arg201Cys or Arg201His) is specifically detected in IPMNs [ 5 , 6 ].…”

“…Ectopic pancreas is basically a benign disease and does not always require resection. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and IPMNs may develop even within ectopic pancreas [ 6 – 21 ]. Therefore, ectopic pancreas might need to be surgically resected depending on the situation.…”

Circulating tumor DNA as a predictive marker for occult metastases in pancreatic cancer patients with radiographically non‐metastatic disease

“…Circulating cell‐free DNA (cfDNA) was extracted from 4 mL of plasma using the QIAamp Circulating Nucleic Acid Kit (QIAGEN), according to the manufacturer’s instructions. Eluted cfDNA was quantified by SYBR Green real‐time PCR analysis of human LINE‐1 sequences, as described elsewhere 23 . A standard curve was obtained using five‐fold serial dilutions of human genomic DNA (Promega).…”

A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms

“…Finally, Hata et al . (2020) demonstrated that the prevalence of GNAS mutations in cfDNA of patients with IPMNs was significantly higher than other pancreatic cystic neoplasms ( Hata et al . 2020 ).…”