Contribution of allelic imbalance to colorectal cancer
| Autor: | Aurora Taira, Emmanouil T. Dermitzakis, Sandeep Kumar Botla, Jussi Taipale, Päivi Sulo, Ulrika A. Hänninen, Bernhard Schmierer, Roosa-Maria Plaketti, Kashyap Dave, Niko Välimäki, Tatiana Cajuso, Torben F. Ørntoft, Anna Vähärautio, Päivi Pihlajamaa, Mervi Aavikko, Maria Sokolova, Halit Ongen, Sari Tuupanen, Johanna Kondelin, Outi Kilpivaara, Anna Lepistö, Kornelia Gladysz, Jukka-Pekka Mecklin, Esa Pitkänen, Eevi Kaasinen, Heli Rauanheimo, Marta Grau, Lauri A. Aaltonen, Mikko P. Turunen, Ari Ristimäki, Linda van den Berg, Riku Katainen, Tuomo Hartonen, Jesper B. Bramsen, Claus L. Andersen, Teemu Kivioja, Tomas Tanskanen, Kimmo Palin, Biswajyoti Sahu, Laura Renkonen-Sinisalo |
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| Přispěvatelé: | Palin, Kimmo [0000-0002-4621-6128], Kivioja, Teemu [0000-0002-7732-2177], Schmierer, Bernhard [0000-0002-9082-7022], Ongen, Halit [0000-0002-4197-5790], Dermitzakis, Emmanouil [0000-0002-9302-6490], Apollo - University of Cambridge Repository, Research Programs Unit, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Doctoral Programme in Integrative Life Science, Centre of Excellence in Stem Cell Metabolism, Nutrient sensing laboratory, Jussi Taipale / Principal Investigator, Institute of Biotechnology, Department of Pathology, HUSLAB, Gastrointestinal tumorigenesis, Clinicum, Doctoral Programme in Clinical Research, Department of Surgery, II kirurgian klinikka, HUS Abdominal Center |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Denmark Loss of Heterozygosity General Physics and Astronomy Allelic Imbalance Loss of heterozygosity Genotype ddc:576.5 RNA Small Interfering lcsh:Science RNA Small Interfering/genetics Genetics Multidisciplinary Genomics Phenotype 3. Good health GENOME syöpägeenit Tumor Suppressor Protein p53/genetics Colorectal Neoplasms Chromosomes Human Pair 8 GENES DNA Copy Number Variations Science Transcription Factors/genetics colorectal cancer Biology Article General Biochemistry Genetics and Molecular Biology Proto-Oncogene Proteins p21(ras) Proto-Oncogene Proteins p21(ras)/genetics 03 medical and health sciences medicine Humans Point Mutation Genetic Predisposition to Disease Gene paksusuolisyöpä Chromosome Aberrations Whole Genome Sequencing HUMAN-COLON Gene Expression Profiling Point mutation Cancer General Chemistry medicine.disease Colorectal Neoplasms/genetics ENHANCERS 030104 developmental biology CELLS lcsh:Q 3111 Biomedicine Tumor Suppressor Protein p53 CRISPR-Cas Systems mutaatiot Transcription Factors Microsatellite Repeats |
| Zdroj: | Palin, K, Pitkänen, E, Turunen, M, Sahu, B, Pihlajamaa, P, Kivioja, T, Kaasinen, E, Välimäki, N, Hänninen, U A, Cajuso, T, Aavikko, M, Tuupanen, S, Kilpivaara, O, van den Berg, L, Kondelin, J, Tanskanen, T, Katainen, R, Grau, M, Rauanheimo, H, Plaketti, R-M, Taira, A, Sulo, P, Hartonen, T, Dave, K, Schmierer, B, Botla, S, Sokolova, M, Vähärautio, A, Gladysz, K, Ongen, H, Dermitzakis, E, Bramsen, J B, Ørntoft, T F, Andersen, C L, Ristimäki, A, Lepistö, A, Renkonen-Sinisalo, L, Mecklin, J-P, Taipale, J & Aaltonen, L A 2018, ' Contribution of allelic imbalance to colorectal cancer ', Nature Communications, vol. 9, 3664 . https://doi.org/10.1038/s41467-018-06132-1 Nature Communications, Vol 9, Iss 1, Pp 1-9 (2018) Nature Communications Nature Communications, Vol. 9, No 1 (2018) P. 3664 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-06132-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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