{"entity":{"id":"paper-larson-cell-free-transcriptome-cancer-nat-commun-2021","kind":"paper","name":"A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection","aka":[],"tldr":"GRAIL's study of RNA in the blood of people with breast and lung cancer, which found tumour genes that are silent in healthy plasma and so stand out.","summary":"In the Circulating Cell-free Genome Atlas cohort (stage III breast cancer 46, lung cancer 30, non-cancer 89), 39,564 of 57,820 annotated genes (68 per cent) were not detected in cell-free RNA from people without cancer. The full text reports that 74 per cent (plus or minus 10) of circulating transcripts in people without cancer come from blood cells; that all four breast cancer patients with FABP7 detected in plasma had tumour fractions above 1 per cent, while the five with the highest apparent tumour fraction had none; that tumour content (tumour fraction times tissue expression) predicted detection better than either alone; and that measuring tumour content \"led to the amplification of cancer-specific signal by orders of magnitude compared to tumor fraction alone\". The authors write that future studies \"will be needed to directly address the potential increase in sensitivity afforded by a multianalyte test\".","asOf":"2026-11-04","links":[{"label":"Larson et al., Nat Commun 2021","url":"https://doi.org/10.1038/s41467-021-22444-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33883548/"}],"tags":[],"related":[],"cancers":["breast-cancer","nsclc"],"sections":["diagnostics","early-detection"],"technologies":["liquid-rna-biopsy","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["biomarker"],"trials":[],"people":[],"bottlenecks":["b-subclone-attribution-residual-disease"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2021,"doi":"10.1038/s41467-021-22444-1","pmid":"33883548","authors":"Larson MH, Pan W, Kim HJ, et al.","paperType":"translational","findings":["68% of annotated genes undetected in non-cancer plasma.","74% (plus or minus 10) of plasma transcripts from blood cells (full text).","Detection of a breast marker tracked tumour fraction times tissue expression (full text)."],"whatItMeans":"Tumour RNA can stand out in blood where a gene is silent in normal plasma, but detection depends on both how much tumour sheds and how strongly the gene is expressed, and it has not been measured below percent-level tumour fractions.","caveats":["Stage III cancers with mostly percent-level tumour fractions.","No limit of detection or parts-per-million figure is given."],"participants":165},"route":"/key-papers/paper-larson-cell-free-transcriptome-cancer-nat-commun-2021/","neighbours":{"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"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":"liquid-rna-biopsy","kind":"technology","name":"Liquid RNA biopsy (cell-free, vesicle and platelet RNA)","route":"/technologies/liquid-rna-biopsy/"}],"term":[{"id":"biomarker","kind":"term","name":"Biomarker","route":"/terms/biomarker/"}],"bottleneck":[{"id":"b-subclone-attribution-residual-disease","kind":"bottleneck","name":"Naming which clone or phenotype is left after treatment","route":"/bottlenecks/b-subclone-attribution-residual-disease/"}],"idea":[{"id":"idea-stack-ctdna-and-tumour-rna-residual-disease","kind":"idea","name":"Read tumour RNA and tumour DNA from the same blood draw to find and type residual cancer","route":"/ideas/idea-stack-ctdna-and-tumour-rna-residual-disease/"}]}}