# Subtype-discordant pancreatic ductal adenocarcinoma tumors show intermediate clinical and molecular characteristics

Source: https://onco.cc/key-papers/paper-topham-subtype-discordant-pancreatic-ccr-2021/  
OnCo record `paper-topham-subtype-discordant-pancreatic-ccr-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Running six published subtype classifiers over 574 tumours, the authors found they agreed in 88% of cases, and the 12% they disagreed on were genuine hybrids with intermediate survival and intermediate KRAS allele imbalance.

## Summary

Sequencing data for 574 pancreatic ductal adenocarcinomas from prospective trials and public databases were classified by six published strategies (Moffitt regression and clustering, Collisson, Bailey, Karasinska). Basal-like and classical calls were concordant in 88% and survival differed by subtype. Twelve percent of tumours were discordant and showed intermediate survival in univariate and multivariate analyses, hybrid expression profiles with classical and basal-like genes co-expressed, and intermediate mutant KRAS allelic imbalance (P < 0.001). Nearly 1 in 6 patients had tumours that failed to fall reliably into either subtype on the two regression tools aimed at clinical practice.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Clinical Cancer Research
- Year: 2021
- DOI: 10.1158/1078-0432.CCR-20-2831
- Authors: Topham JT, Karasinska JM, Lee MKC, et al.
- Findings: 88% concordance between classifiers; 12% discordant hybrids.; Hybrids show intermediate survival and intermediate KRAS allelic imbalance.
- What it means: A subtype report should carry a confidence, and a trial that dichotomises subtype will misplace about one patient in eight.
- Caveats: Retrospective; mixed platforms.; No treatment assignment by subtype.

## Sources

- Topham et al., Clin Cancer Res 2021: subtype-discordant tumours in 574 cases: https://doi.org/10.1158/1078-0432.CCR-20-2831
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33051307/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- institutions: [BC Cancer](https://onco.cc/institutions/bc-cancer/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)

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