# Label every targetable mutation as truncal or branch on the report

Source: https://onco.cc/ideas/idea-bio1-truncal-branch-labelling/  
OnCo record `idea-bio1-truncal-branch-labelling` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A drug aimed at a mutation present in every tumour cell works differently from one aimed at a mutation in only some cells. Test reports should say which is which.

## Summary

Tumour sequencing reports list alterations without their cancer cell fraction. Adding a clonality estimate (truncal, subclonal with estimated fraction, indeterminate) is computationally routine from purity- and copy-number-adjusted VAFs. Trials could then stratify by clonality and drug labels could state that benefit was shown for clonal alterations.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Patients whose targetable alteration is subclonal have materially shorter progression-free survival on the matched drug than those with a clonal alteration, and reporting clonality shifts prescribing toward combinations in the subclonal group.
- Rationale: Subclonal targets predict poor responses in lung, colorectal and breast cohorts; the field ignores this because reports do not surface it. It costs nothing to compute.
- Proposed test: Re-analyse the sequencing from three completed targeted-therapy trials to estimate the clonal versus subclonal hazard ratio; if confirmed, pilot clonality labelling with two commercial panel providers and audit prescribing changes.
- Maturity: preclinical-evidence
- Actor: data

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/)
- companies: [Foundation Medicine (Roche)](https://onco.cc/companies/foundation-medicine/), [Guardant Health](https://onco.cc/companies/guardant-health/), [Tempus AI](https://onco.cc/companies/tempus/)
- terms: [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [Variant allele frequency (VAF)](https://onco.cc/terms/vaf/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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