| Autor: |
Palin, Kimmo, Pitkänen, Esa, Turunen, Mikko, Sahu, Biswajyoti, Pihlajamaa, Päivi, Kivioja, Teemu, Kaasinen, Eevi, Välimäki, Niko, Hänninen, Ulrika A., Cajuso, Tatiana, Aavikko, Mervi, Tuupanen, Sari, Kilpivaara, Outi, van den Berg, Linda, Kondelin, Johanna, Tanskanen, Tomas, Katainen, Riku, Grau, Marta, Rauanheimo, Heli, Plaketti, Roosa-Maria |
| Zdroj: |
Nature Communications; 9/10/2018, Vol. 9 Issue 1, p1-1, 1p |
| Abstrakt: |
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. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate 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. In this study the authors examine the allelic imbalance (AI) landscape of colorectal cancer, reporting loss of TP53 as a driver of AI. They use CRISPR-Cas9 screens to identify 79 genes (within AI regions) regulating cell growth and identify a network of transcription factors that may contribute to colorectal tumorigenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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