FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA

Cancer Research, Journal Year: 2024, Volume and Issue: 84(10), P. 1560 - 1569

Published: March 14, 2024

Abstract Genomic analysis of the T-cell receptor (TCR) reveals strength, breadth, and clonal dynamics adaptive immune response to pathogens or cancer. The diversity TCR repertoire, however, means that sequencing is technically challenging, particularly for samples with low-quality, degraded nucleic acids. Here, we developed validated FUME-TCRseq, a robust sensitive RNA-based methodology suitable formalin-fixed paraffin-embedded low amounts input material. FUME-TCRseq incorporates unique molecular identifiers into each molecule cDNA, allowing correction errors PCR bias. Using RNA extracted from colorectal head neck cancers benchmark accuracy sensitivity against existing methods demonstrated excellent concordance between datasets. Furthermore, detected more clonotypes than commercial alternative, shorter library preparation time significantly lower cost. high ability sequence poor quality limited amount enabled quantitative small numbers cells archival tissue sections, which not possible other methods. Spatially resolved using macrodissected revealed shifting landscapes at transition an invasive phenotype tumor subclones containing distinct driver alterations. In summary, represents accurate, sensitive, low-cost tool characterization repertoires, in low-quality have been accessible methodology. Significance: supports spatially detection clones clinical specimens, can facilitate longitudinal tracking responses through disease course treatment.

Language: Английский

The impact of elective cervical lymph node treatment on the tumour immune response in head and neck squamous cell carcinoma: time for a change in treatment strategy?

BJC Reports, Journal Year: 2024, Volume and Issue: 2(1)

Published: Sept. 9, 2024

Language: Английский