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TRACERx: TRAcking non-small cell lung Cancer Evolution through therapy (Rx). Pilot Study. Multi-region sequencing of early-stage NSCLCs.

Deciphering the complexity of non-small cell lung cancer (NSCLC) evolutionary histories may elucidate the basis for its dismal outcome. We performed multi-region sequencing of early-stage NSCLCs. Spatial dissection revealed branched tumor evolution, with driver mutations occurring before and after subclonal diversification. Intra-tumor heterogeneity in DNA copy number alterations, translocations and endogenous APOBEC mutational processes demonstrates that NSCLC may follow multiple distinct evolutionary trajectories simultaneously. In smokers, despite maintained carcinogen exposure, temporal dissection reveals a relative decrease in smoking-related mutations during tumor progression, accompanied by an increase in APOBEC-related mutations. In the tumors from ex-smokers, genome-doubling occurred before subclonal diversification, suggesting prolonged latency before clinical detection. Multi-region sequencing demonstrates the relentless and heterogeneous nature of genomic instability processes in early-stage NSCLCs.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001000900 Illumina Genome Analyzer IIx Illumina HiSeq 2000 Illumina HiSeq 2500 Ion Torrent PGM 28
EGAD00001001918 Illumina HiSeq 1000 15
Publications Citations
Spatial and temporal diversity in genomic instability processes defines lung cancer evolution.
Science 346: 2014 251-256
658
DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution.
Genome Biol 17: 2016 31
610
Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade.
Science 351: 2016 1463-1469
1639
Between-region genetic divergence reflects the mode and tempo of tumor evolution.
Nat Genet 49: 2017 1015-1024
75
Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing.
Nat Commun 9: 2018 216
76
Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy.
Nat Commun 10: 2019 657
27