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Contribution of all...
Contribution of allelic imbalance to colorectal cancer
- Article/chapterEnglish2018
Publisher, publication year, extent ...
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2018-09-10
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Springer Science and Business Media LLC,2018
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:139128740
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http://kipublications.ki.se/Default.aspx?queryparsed=id:139128740URI
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https://doi.org/10.1038/s41467-018-06132-1DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Added entries (persons, corporate bodies, meetings, titles ...)
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Pitkanen, E
(author)
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Turunen, M
(author)
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Sahu, B
(author)
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Pihlajamaa, P
(author)
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Kivioja, T
(author)
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Kaasinen, E
(author)
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Valimaki, N
(author)
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Hanninen, UA
(author)
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Cajuso, T
(author)
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Aavikko, M
(author)
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Tuupanen, S
(author)
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Kilpivaara, O
(author)
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van den Berg, L
(author)
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Kondelin, J
(author)
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Tanskanen, T
(author)
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Katainen, R
(author)
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Grau, M
(author)
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Rauanheimo, H
(author)
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Plaketti, RM
(author)
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Taira, A
(author)
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Sulo, P
(author)
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Hartonen, T
(author)
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Dave, KKarolinska Institutet
(author)
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Schmierer, BKarolinska Institutet
(author)
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Botla, SKarolinska Institutet
(author)
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Sokolova, M
(author)
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Vaharautio, A
(author)
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Gladysz, K
(author)
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Ongen, H
(author)
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Dermitzakis, E
(author)
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Bramsen, JB
(author)
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Orntoft, TF
(author)
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Andersen, CL
(author)
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Ristimaki, A
(author)
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Lepisto, A
(author)
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Renkonen-Sinisalo, L
(author)
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Mecklin, JP
(author)
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Taipale, JKarolinska Institutet
(author)
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Aaltonen, LAKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Nature communications: Springer Science and Business Media LLC9:1, s. 3664-2041-1723
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- By the author/editor
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Palin, K
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Pitkanen, E
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Turunen, M
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Sahu, B
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Pihlajamaa, P
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Kivioja, T
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show more...
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Kaasinen, E
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Valimaki, N
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Hanninen, UA
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Cajuso, T
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Aavikko, M
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Tuupanen, S
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Kilpivaara, O
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van den Berg, L
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Kondelin, J
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Tanskanen, T
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Katainen, R
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Grau, M
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Rauanheimo, H
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Plaketti, RM
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Taira, A
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Sulo, P
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Hartonen, T
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Dave, K
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Schmierer, B
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Botla, S
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Sokolova, M
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Vaharautio, A
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Gladysz, K
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Ongen, H
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Dermitzakis, E
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Bramsen, JB
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Orntoft, TF
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Andersen, CL
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Ristimaki, A
-
Lepisto, A
-
Renkonen-Sinisal ...
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Mecklin, JP
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Taipale, J
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Aaltonen, LA
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Karolinska Institutet