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Sequencing 148 samples from cysts and the small cancers beside them established that both IPMNs and mucinous cystic neoplasms are true precursors, and that SMAD4 and TGFBR2 mutations mark the step into invasion, with about three years between high-grade dysplasia and cancer.
148 samples from IPMNs, mucinous cystic neoplasms and small associated invasive carcinomas from 18 patients were analysed by whole-exome or targeted sequencing. Evolutionary analyses established both IPMNs and MCNs as direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 were frequently restricted to the invasive carcinoma while RNF43 alterations were largely in the non-invasive lesions. Genomic analyses suggested an average window of over three years between the development of high-grade dysplasia and pancreatic cancer.
It gives surveillance a target and a timetable: catch high-grade dysplasia and there are about three years before invasion, and TGF-beta pathway loss is the event to detect.
Shares High-risk pancreatic surveillance (CAPS / PRECEDE), Clonal evolution & minimal residual disease, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
Shares RNF43, SMAD4, Clonal evolution & minimal residual disease, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors.
Shares RNF43, Wnt / β-catenin, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
Shares RNF43, Nature Communications, Wnt / β-catenin, Whole-exome & whole-genome sequencing.
Shares High-risk pancreatic surveillance (CAPS / PRECEDE), Clonal evolution & minimal residual disease, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Whole-exome & whole-genome sequencing.
Shares SMAD4, Clonal evolution & minimal residual disease, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Pancreatic ductal adenocarcinoma.
Shares RNF43, SMAD4, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
Shares TGFBR2, SMAD4, TGF-β signalling, Whole-exome & whole-genome sequencing.