# A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma

Source: https://onco.cc/key-papers/paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020/  
OnCo record `paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sampling several regions of metastatic pancreatic cancers showed that squamous-looking areas are the tissue form of the basal-like gene signature, usually a subclone inside an otherwise classical tumour, and that such cancers carry chromatin-gene mutations and uneven MYC gain.

## Summary

Evolutionary analysis and expression profiling were integrated in multiregion-sampled metastatic pancreatic cancers. Squamous features were the histological correlate of the RNA-seq-defined basal-like subtype. In patients with coexisting basal-squamous and classical-glandular morphology, phylogenetics showed squamous morphology as a subclonal population within an otherwise classical tumour. Cancers with squamous features were more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification and entosis.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature Cancer
- Year: 2020
- DOI: 10.1038/s43018-019-0010-1
- Authors: Hayashi A, Fan J, Chen R, et al.
- Findings: Squamous histology is the tissue correlate of basal-like expression and usually subclonal.; Squamous-feature cancers carry clonal chromatin-modifier mutations and heterogeneous MYC amplification.
- What it means: It joins the pathology (adenosquamous), the transcriptome (basal-like) and the genome (KDM6A, MYC) into one account of the chemotherapy-resistant subtype, and shows a single biopsy can miss it.
- Caveats: Rapid-autopsy metastatic cohort.; Entosis and MYC heterogeneity are descriptive findings.

## Sources

- Hayashi et al., Nat Cancer 2020: squamous features are the histological correlate of basal-like expression: https://doi.org/10.1038/s43018-019-0010-1
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35118421/

## Connected records

- cancers: [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- targets: [KDM6A](https://onco.cc/targets/kdm6a/), [MYC](https://onco.cc/targets/myc-gene/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [MYC](https://onco.cc/pathways/myc/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/)
- journals: [Nature Cancer](https://onco.cc/journals/nature-cancer/)

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