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Evolutionary dynamics in the decades preceding acute myeloid leukaemia

Somatic evolution in ageing tissues underlies many cancers, yet the quantitative rules governing pre-cancerous evolution remain incompletely understood. This study exploits a collection of serial blood serum samples from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), collected annually from as early as 15 years before a diagnosis of acute myeloid leukaemia (AML), to provide a quantitative description of pre-cancerous evolutionary dynamics. Longitudinal samples from women who subsequently developed AML, alongside timepoint-matched samples from age-matched cancer-free controls, were sequenced using TETRIS-seq, a deep duplex error-corrected sequencing approach covering a custom panel of single-nucleotide variants and indels, mosaic chromosomal alterations, and chromosomal rearrangements associated with clonal haematopoiesis and AML. Combined with evolutionary modelling, these data quantify the acquisition ages and fitness effects of key driver events in AML development, characterise the clonal dynamics that precede diagnosis, and show that pre-leukaemic evolution is consistent with a small set of evolutionary rules balancing chance and determinism. The deposited data comprise raw paired-end FASTQ files for all sequenced samples.

Type: Cancer Genomics
Archive: European Genome-phenome Archive (EGA)

2 Datasets

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
EGAD50000003110	Targeted duplex sequencing (TETRIS-seq) of a custom ~58 kb hybrid-capture panel covering commonly mutated exons across 34 clonal haematopoiesis and AML-associated genes, applied to 496 longitudinal blood samples from women in the UKCTOCS trial who subsequently developed acute myeloid leukaemia and from matched controls who did not. The dataset comprises 467 paired-end FASTQ runs sequenced on the Illumina NovaSeq 6000, together with 29 unaligned per-sample BAM files with unique molecular identifiers for one sequencing pool, where demultiplexing produced per-sample BAM files rather than per-sample FASTQ files. Also included are per-sample VCF files reporting the variant calling output at every position covered by the panel, from both single-strand and duplex consensus sequences, germline SNV and indel calls across the cohort, and sample-level metadata giving unrounded ages and sample collection timings. Associated with Watson et al., Evolutionary dynamics in the decades preceding acute myeloid leukaemia.	Illumina NovaSeq 6000	496
EGAD50000003111	Targeted duplex sequencing (TETRIS-seq) of a custom ~1.6 Mb hybrid-capture panel for the detection of mosaic chromosomal alterations, chromosomal rearrangements and KMT2A partial tandem duplications, applied to longitudinal blood samples from women in the UKCTOCS trial who subsequently developed acute myeloid leukaemia and from matched controls who did not. The dataset comprises 316 paired-end FASTQ runs sequenced on the Illumina NovaSeq 6000, together with 30 unaligned per-sample BAM files with unique molecular identifiers for one sequencing pool, where demultiplexing produced per-sample BAM files rather than per-sample FASTQ files. Also included are per-SNP B-allele frequency and log R ratio files for the 130 sample-timepoints underlying the mosaic chromosomal alteration calls, and sample-level metadata giving unrounded ages and sample collection timings. Associated with Watson et al., Evolutionary dynamics in the decades preceding acute myeloid leukaemia.	Illumina NovaSeq 6000	496