# Precancerous neoplastic cells can move through the pancreatic ductal system

Source: https://onco.cc/key-papers/paper-makohon-moore-precursor-cells-ductal-system-nature-2018/  
OnCo record `paper-makohon-moore-precursor-cells-ductal-system-nature-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing several precursor lesions and the cancer from the same pancreas showed that what look like separate high-grade lesions are often one neoplasm that has crawled along the duct system over years.

## Summary

Somatic variants of pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas were analysed. Evolutionary inference showed an ancestral cell initiating and clonally expanding to form one or more lesions, with subsequent driver mutations eventually leading to invasive cancer, a multi-step progression generally spanning many years. Independent high-grade precursor lesions observed in a single pancreas often represent a single neoplasm that has colonised the ductal system, accumulating spatial and genetic divergence.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature
- Year: 2018
- DOI: 10.1038/s41586-018-0481-8
- Authors: Makohon-Moore AP, Matsukuma K, Zhang M, et al.
- Findings: Apparently independent high-grade precursor lesions are often one neoplasm colonising the ducts.; Progression from ancestral cell to invasive cancer spans many years.
- What it means: It reframes multifocal high-grade dysplasia found at surveillance: the pancreas may hold one spreading lesion rather than several, which bears on how much gland to remove.
- Caveats: Small number of pancreata analysed regionally.; Timing estimates rest on molecular clock assumptions.

## Sources

- Makohon-Moore et al., Nature 2018: precancerous cells move through the ductal system: https://doi.org/10.1038/s41586-018-0481-8
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30177826/

## Connected records

- cancers: [Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors](https://onco.cc/cancers/ipmn-cystic-precursors/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [High-risk pancreatic surveillance (CAPS / PRECEDE)](https://onco.cc/technologies/pancreatic-surveillance/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/)
- journals: [Nature](https://onco.cc/journals/nature/)

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