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Excited to share our study (led by @noemichael ) reporting comprehensive genomic analysis of neoplastic pancreatic cysts and associated #PancreaticCancer in @NatureComms . So many crucial collaborators in the @pbpath community shared cases for analysis. https://www.nature.com/articles/s41467-020-17917-8
Several important findings:
1. Evolutionary analyses revealed IPMNs and MCNs are true precursors to invasive cancer.
1. Evolutionary analyses revealed IPMNs and MCNs are true precursors to invasive cancer.
2. Mutations in SMAD4 and TGFBR2 were often limited to invasive cancers and absent from precancerous components, highlighting the role of TGFB pathway dysregulation in driving PDAC invasion.
3. Mutations in RNF43 were often limited to subclones in IPMNs/MCNs that did not invade, and there were often multiple, mutually exclusive subclonal RNF43 mutations in single IPMNs/MCNs. This suggests convergent evolution and complex selective forces on RNF43 mutations.
4. Molecular clock analyses suggest >3 years between the development of high-grade dysplasia and transformation to invasive cancer, highlighting a window of opportunity for early detection.
Tagging coauthors @NoushinNiknafs @peaantonio1 @CaDxPath @KarchinRachel @velculescu @marijadebeljak @JordanMWinterMD for their outstanding contributions.
Could not have done this work outside of the incredible academic environment of @JHUPath @Hopkins_GI_Path !
