# A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection

Source: https://onco.cc/key-papers/paper-larson-cell-free-transcriptome-cancer-nat-commun-2021/  
OnCo record `paper-larson-cell-free-transcriptome-cancer-nat-commun-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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".

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: Nature Communications
- Year: 2021
- DOI: 10.1038/s41467-021-22444-1
- Authors: Larson MH, Pan W, Kim HJ, et al.
- 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).
- What it means: 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.

## Sources

- Larson et al., Nat Commun 2021: https://doi.org/10.1038/s41467-021-22444-1
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33883548/

## Connected records

- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Liquid RNA biopsy (cell-free, vesicle and platelet RNA)](https://onco.cc/technologies/liquid-rna-biopsy/)
- terms: [Biomarker](https://onco.cc/terms/biomarker/)
- bottlenecks: [Naming which clone or phenotype is left after treatment](https://onco.cc/bottlenecks/b-subclone-attribution-residual-disease/)
- ideas: [Read tumour RNA and tumour DNA from the same blood draw to find and type residual cancer](https://onco.cc/ideas/idea-stack-ctdna-and-tumour-rna-residual-disease/)

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