For our BAP1 manuscript
How cell-to-cell copy number alterations that underpin genomic instability in human cancers drive genomic and phenotypic variation, and consequently cancer evolution, remains understudied. Here, applying scaled single cell whole genome sequencing to wildtype, TP53-deficient and TP53/BRCA1/2-deficient mammary epithelial cells (n=13,818 genomes) and primary triple negative breast (TNBC) and high grade serous ovarian cancers (HGSC) (n=22,057 genomes), we identified three distinct ‘foreground’ mutational patterns defined by cell-to-cell copy number and structural variation properties occurring in the ‘background’ of cancer-associated genomic instability. Cell and clone-specific high level amplifications (HLAMPs), parallel allele-specific copy number alterations and copy number segment length variation (serrate structural variations) exhibited measurable phenotypic and evolutionary consequences. Clone-specific HLAMPs in known oncogenes were highly prevalent in fold back inversion (FBI)-bearing tumors and associated with increased clone-to-clone phenotypic variation in gene expression inferred from matched single cell RNASeq. Parallel allele-specific alterations were linked with phylogenetically determined evolutionary diversity and clone-specific mono-allelic expression. Serrate patterns present across all clones were increased in FBI tumors, most prominently on a tetraploid background and were highly correlated with increased genomic diversity of cellular populations. Taken together, we show that cell-to-cell structural-copy number variation significantly impacts the phenotypes and evolutionary diversity of TNBC and HGSC, revealing previously hidden genomic states of cancer cells.
The dataset encompasses 1110 Runs from the WGSPD Project 3 - Genomic Strategies to Identify High-impact Psychiatric Risk Variants Project
The dataset encompasses 804 Runs from the WGSPD Project 3 - Genomic Strategies to Identify High-impact Psychiatric Risk Variants Project
The ERDERA Diagnostic Research Workstream DAC decides on data access requests according to the principles defined in the ERDERA Data Sharing Framework Agreement.
Whole exome sequencing of infant high grade gliomas. BAM files of paired end reads aligned to GRCh37 with bwa
Illumina whole genome sequencing to high depth (x50) of four Tanzanian individuals. Genomic DNA derived from peripheral whole blood.
