{"entity":{"id":"paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","kind":"paper","name":"Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumour DNA","aka":["Scherer 2016","CAPP-Seq in lymphoma","Circulating tumour DNA genotyping of cell of origin"],"tldr":"A blood test read the genetic type of a lymphoma without a biopsy, detected disease left behind better than scans did, and spotted the change from a slow lymphoma into an aggressive one before it showed.","summary":"Scherer, Kurtz, Alizadeh and Diehn applied cancer personalised profiling by deep sequencing to tumour biopsies and cell-free DNA from 92 lymphoma patients and 24 healthy subjects. The results set out most of what circulating tumour DNA can do in this disease.\n\nAt diagnosis the amount of circulating tumour DNA correlated strongly with clinical indices and independently predicted outcome. Genotyping the plasma classified transcriptionally defined tumour subtypes, including the cell of origin of diffuse large B-cell lymphoma, directly from blood. Tracking multiple somatic mutations at once outperformed immunoglobulin sequencing and radiographic imaging for detecting minimal residual disease, and identified emergent resistance mutations to targeted therapies without a biopsy. Distinct patterns of clonal evolution separated follicular lymphomas that stayed indolent from those that transformed into diffuse large B-cell lymphoma, which raises the possibility of predicting histological transformation non-invasively.\n\nThat last finding is the one with the most direct consequence for patients, because transformation is the event that turns a disease people live with into one that can kill quickly, and it is currently found only by re-biopsying someone who has already deteriorated.","asOf":"2026-10-01","links":[{"label":"Science Translational Medicine 2016","url":"https://doi.org/10.1126/scitranslmed.aai8545"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27831904/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27831904"}],"tags":["lymphoma-evidence"],"related":["paper-kurtz-j-clin-oncol","paper-kurtz-nat-biotechnol","lymphoma-roadmap"],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy","ngs","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","cell-of-origin"],"trials":[],"people":["ash-alizadeh"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-early-detection"],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2016,"doi":"10.1126/scitranslmed.aai8545","pmid":"27831904","authors":"Scherer F, Kurtz DM, Newman AM, et al.","paperType":"translational","findings":["Circulating tumour DNA was profiled by cancer personalised profiling by deep sequencing in 92 lymphoma patients and 24 healthy subjects.","The amount of circulating tumour DNA at diagnosis correlated strongly with clinical indices and independently predicted outcome.","Circulating tumour DNA genotyping classified transcriptionally defined tumour subtypes, including diffuse large B-cell lymphoma cell of origin, directly from plasma.","Simultaneous tracking of multiple somatic mutations outperformed immunoglobulin sequencing and radiographic imaging for detecting minimal residual disease.","Distinct patterns of clonal evolution distinguished indolent follicular lymphomas from those that transformed into diffuse large B-cell lymphoma."],"whatItMeans":"The paper that established lymphoma as the solid-tumour field where circulating tumour DNA works best, because the mutations are many and the tumour sheds. It underpins the response-adapted trial designs now being built on molecular rather than radiographic response.","caveats":["92 patients across several lymphoma types; subgroup findings rest on small numbers.","No trial has yet acted on a circulating tumour DNA result in lymphoma and shown that doing so improves survival.","The assay was a research platform; commercial implementations differ in sensitivity and in the mutations they track.","Transformation prediction was demonstrated retrospectively in a small set and has not been validated prospectively."],"changedPractice":false,"participants":116},"route":"/key-papers/paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016/","neighbours":{"paper":[{"id":"paper-kurtz-j-clin-oncol","kind":"paper","name":"Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma","route":"/key-papers/paper-kurtz-j-clin-oncol/"},{"id":"paper-kurtz-nat-biotechnol","kind":"paper","name":"Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA","route":"/key-papers/paper-kurtz-nat-biotechnol/"},{"id":"paper-cheson-j-clin-oncol","kind":"paper","name":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification","route":"/key-papers/paper-cheson-j-clin-oncol/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"term":[{"id":"cell-of-origin","kind":"term","name":"Cell of origin (GCB vs ABC)","route":"/terms/cell-of-origin/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"person":[{"id":"ash-alizadeh","kind":"person","name":"Ash A. Alizadeh","route":"/people/ash-alizadeh/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","route":"/bottlenecks/b-early-detection/"}],"journal":[{"id":"science-translational-medicine","kind":"journal","name":"Science Translational Medicine","route":"/journals/science-translational-medicine/"}],"idea":[{"id":"lymphoma-ev-ctdna-instead-of-the-interim-scan","kind":"idea","name":"Use circulating tumour DNA instead of the interim scan to decide what happens next","route":"/ideas/lymphoma-ev-ctdna-instead-of-the-interim-scan/"}]}}