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Contribution of allelic imbalance to colorectal cancer

Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge, and unbiased CRISPR-Cas9 knockout and activation screens identified altogether 79 genes within AI peaks regulating cell growth. Genetic and functional data implicates loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.

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
EGAD00001004098 Illumina HiSeq 2000 Illumina HiSeq 4000 426
EGAD00001004099 Illumina HiSeq 4000 23
EGAD00001004100 HiSeq X Ten Illumina HiSeq 2500 8
EGAD00010001566 humanomniexpress-24-v1-1-a 2
Publications Citations
Contribution of allelic imbalance to colorectal cancer.
Nat Commun 9: 2018 3664
Sequence determinants of human gene regulatory elements.
Nat Genet 54: 2022 283-294
A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites.
Nat Biotechnol 41: 2023 197-203