PT  - JOURNAL ARTICLE
AU  - Marc J Williams
AU  - Tyler Funnell
AU  - Ciara H O’Flanagan
AU  - Andrew McPherson
AU  - Sohrab Salehi
AU  - Ignacio Vázquez-García
AU  - Farhia Kabeer
AU  - Hakwoo Lee
AU  - Tehmina Masud
AU  - Peter Eirew
AU  - Damian Yap
AU  - Beixi Wang
AU  - Jazmine Brimhall
AU  - Justina Biele
AU  - Jerome Ting
AU  - Sean Beatty
AU  - Daniel Lai
AU  - Jenifer Pham
AU  - Diljot Grewal
AU  - Douglas Abrams
AU  - Eliyahu Havasov
AU  - Samantha Leung
AU  - Viktoria Bojilova
AU  - Adam C Weiner
AU  - Nicole Rusk
AU  - Florian Uhlitz
AU  - Nicholas Ceglia
AU  - IMAXT consortium
AU  - Samuel Aparicio
AU  - Sohrab P. Shah
TI  - Evolutionary tracking of cancer haplotypes at single-cell resolution
AID  - 10.1101/2021.06.04.447031
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.04.447031
4099  - http://biorxiv.org/content/early/2021/06/06/2021.06.04.447031.short
4100  - http://biorxiv.org/content/early/2021/06/06/2021.06.04.447031.full
AB  - Cancer genomes exhibit extensive chromosomal copy number changes and structural variation, yet how allele specific alterations drive cancer genome evolution remains unclear. Here, through application of a new computational approach we report allele specific copy number alterations in 11,097 single cell whole genomes from genetically engineered mammary epithelial cells and 21,852 cells from high grade serous ovarian and triple negative breast cancers. Resolving single cell copy number profiles to individual alleles uncovered genomic background distributions of gains, losses and loss of heterozygosity, yielding evidence of positive selection of specific chromosomal alterations. In addition specific genomic loci in maternal and paternal alleles were commonly found to be altered in parallel with convergent phenotypic transcriptional effects. Finally we show that haplotype specific alterations trace the cyclical etiology of high level amplifications and reveal clonal haplotype decomposition of complex structures. Together, our results illuminate how allele and haplotype specific alterations, here determined across thousands of single cell cancer genomes, impact the etiology and evolution of structural variations in human tumours.Competing Interest StatementSPS and SA are shareholders and consultants of Canexia Health Inc.