# Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer

Source: https://onco.cc/key-papers/paper-makohon-moore-metastases-driver-homogeneity-nat-genet-2017/  
OnCo record `paper-makohon-moore-metastases-driver-homogeneity-nat-genet-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Deep sequencing of 26 separate metastases from four patients found the same driver mutations in every one, so a biopsy of any single site should represent the whole disease for targeted therapy.

## Summary

Sixty-fold whole-genome sequencing of 26 metastases from four patients with pancreatic cancer showed identical mutations in known driver genes in every metastatic lesion for each patient. Passenger mutations accounted for all intratumoural heterogeneity, and even among those the genetic similarity of founding cells was higher than expected for two randomly chosen normal cells.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature Genetics
- Year: 2017
- DOI: 10.1038/ng.3764
- Authors: Makohon-Moore AP, Zhang M, Reiter JG, et al.
- Findings: Identical driver mutations in all 26 metastases across four patients.; Heterogeneity was confined to passenger mutations.
- What it means: Encouraging for targeted therapy: unlike some cancers, the drivers do not differ between deposits, so one biopsy is enough to choose a RAS or repair-directed drug.
- Caveats: Four patients from a rapid autopsy programme.; Treatment-naive metastases; therapy can add resistance mutations.

## Sources

- Makohon-Moore et al., Nat Genet 2017: limited driver heterogeneity among 26 metastases from four patients: https://doi.org/10.1038/ng.3764
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28092682/

## Connected records

- cancers: [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [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/)
- people: [Bert Vogelstein](https://onco.cc/people/bert-vogelstein/)
- journals: [Nature Genetics](https://onco.cc/journals/nature-genetics/)

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