# KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer

Source: https://onco.cc/terms/kras-allelic-imbalance/  
OnCo record `kras-allelic-imbalance` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Beyond which KRAS mutation a pancreatic tumour carries, how many copies of the mutant allele it has matters: tumours that lose the normal copy or gain extra mutant copies behave more aggressively and lean towards the basal-like subtype, which is one reason two tumours with the same KRAS mutation can look and behave differently.

## Summary

Whole-genome sequencing of purified tumour samples in the COMPASS and PanCuRx programmes showed that the balance between the mutant and wild-type KRAS alleles is itself a variable: minor imbalance (more mutant than wild-type copies) and major imbalance (loss of the wild-type allele, often with gain of the mutant one) were associated with the basal-like transcriptional programmes and with worse outcome, while balanced tumours were more often classical (Chan-Seng-Yue 2020). The same study found that classical and basal-like are a continuum, with about 12% of tumours hybrid and intermediate in survival, and that squamous histology is the tissue form of the basal-like signature, often as a subclone. Punctuated evolution explains how imbalance arises: two-thirds of pancreatic cancer genomes show chromothripsis or polyploidy that can change copy number of several drivers at once rather than by stepwise mutation (Notta 2016). In practice routine reports often say only KRAS mutant; allele-level reporting (G12D, G12V, G12R, G12C, Q61) decides which RAS inhibitor applies and carries prognosis, and copy number adds a further layer that no test in routine use reports (the record's open problems). The KRAS allele shares on the record are counts of mutation records over all KRAS mutation records in each cohort.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: KRAS allelic imbalance; Mutant KRAS dosage; Loss of wild-type KRAS; KRAS major imbalance; KRAS copy gain
- Tags: pancreatic-molecular

## Sources

- Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes): https://doi.org/10.1038/s41588-019-0566-9
- Notta et al., Nature 2016: a renewed, punctuated model of pancreatic cancer evolution: https://doi.org/10.1038/nature19823

## Connected records

- biomarkers: [KRAS G12D (and other non-G12C KRAS mutations)](https://onco.cc/biomarkers/kras-g12d/)
- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- terms: [Classical versus basal-like (squamous) subtypes of pancreatic cancer, and GATA6](https://onco.cc/terms/classical-vs-basal-like/), [COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection](https://onco.cc/terms/compass-study-pancreatic/), [Copy number alteration (CNA)](https://onco.cc/terms/copy-number-variation-term/), [GATA6 as the marker of classical versus basal-like pancreatic cancer](https://onco.cc/terms/gata6-classical-basal-marker/), [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/), [Whole-genome doubling (WGD)](https://onco.cc/terms/whole-genome-doubling/)
- key papers: [A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns](https://onco.cc/key-papers/paper-notta-punctuated-evolution-pancreatic-nature-2016/), [Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution](https://onco.cc/key-papers/paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020/)

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