{"entity":{"id":"idea-bio1-truncal-branch-labelling","kind":"idea","name":"Label every targetable mutation as truncal or branch on the report","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp"],"targets":[],"drugs":[],"companies":["foundation-medicine","tempus","guardant-health"],"institutions":[],"pathways":[],"terms":["vaf","ngs"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"small","horizonYears":2},"route":"/ideas/idea-bio1-truncal-branch-labelling/","neighbours":{"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"}],"company":[{"id":"foundation-medicine","kind":"company","name":"Foundation Medicine (Roche)","route":"/companies/foundation-medicine/"},{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/"},{"id":"tempus","kind":"company","name":"Tempus AI","route":"/companies/tempus/"}],"term":[{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"vaf","kind":"term","name":"Variant allele frequency (VAF)","route":"/terms/vaf/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}