ArticleNature communications2018
Contribution of allelic imbalance to colorectal cancer.
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Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
1.4field-weighted citation impact, top 21% of its field
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
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- Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer.Science advances · 2025Article
- Pan-cancer copy number analysis identifies optimized size thresholds and co-occurrence models for individualized risk stratification.Nature communications · 2025Article
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- Cytogenetic signatures favoring metastatic organotropism in colorectal cancer.Nature communications · 2025Article
- KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition.Cancer research · 2025Article
- Lynch syndrome-associated and sporadic microsatellite unstable colorectal cancers: different patterns of clonal evolution yield highly similar tumours.Human molecular genetics · 2024Article
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- Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.Nature genetics · 2024Article
- CRISPR/Cas9: a powerful tool in colorectal cancer research.Journal of experimental & clinical cancer research : CR · 2023Review
- A competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites.Nature biotechnology · 2023Article
- Copy Number Variations as Determinants of Colorectal Tumor Progression in Liquid Biopsies.International journal of molecular sciences · 2023Review
- Association between germline variants and somatic mutations in colorectal cancer.Scientific reports · 2022Article
- Copy Number Alterations as Novel Biomarkers and Therapeutic Targets in Colorectal Cancer.Cancers · 2022Review
- Follow-up of tissue genomics in BRCA1/2 carriers who underwent prophylactic surgeries.Breast cancer (Tokyo, Japan) · 2021Article
- The expressed mutational landscape of microsatellite stable colorectal cancers.Genome medicine · 2021Article
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- Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine.Non-coding RNA · 2021Review
Corrections and comments
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Authors and funding
40 authors at 5 institutions in 5 countries.
Kimmo PalinDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.ORCID http://orcid.org/0000-0002-4621-6128
Esa PitkänenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Mikko TurunenGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Biswajyoti SahuGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Päivi PihlajamaaGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Teemu KiviojaGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.ORCID http://orcid.org/0000-0002-7732-2177
Eevi KaasinenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Niko VälimäkiDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Ulrika A HänninenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Tatiana CajusoDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Mervi AavikkoDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Sari TuupanenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Outi KilpivaaraDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Linda van den BergDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Johanna KondelinDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Tomas TanskanenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Riku KatainenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Marta GrauDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Heli RauanheimoDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Roosa-Maria PlakettiDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Aurora TairaDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Päivi SuloDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Tuomo HartonenGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Kashyap DaveDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, SE-17165, Stockholm, Sweden.
Bernhard SchmiererDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, SE-17165, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-9082-7022
Sandeep BotlaDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, SE-17165, Stockholm, Sweden.
Maria SokolovaGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Anna VähärautioGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Kornelia GladyszDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Halit OngenGenetic Medicine and Development, University of Geneva Medical School-CMU, 1 Rue Michel-Servet, 1211, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-4197-5790
Emmanouil DermitzakisGenetic Medicine and Development, University of Geneva Medical School-CMU, 1 Rue Michel-Servet, 1211, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-9302-6490
Jesper Bertram BramsenDepartment of Molecular Medicine, Aarhus University Hospital, DK8200, Aarhus N, Denmark.
Torben Falck ØrntoftDepartment of Molecular Medicine, Aarhus University Hospital, DK8200, Aarhus N, Denmark.
Claus Lindbjerg AndersenDepartment of Molecular Medicine, Aarhus University Hospital, DK8200, Aarhus N, Denmark.
Ari RistimäkiGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland.
Anna LepistöDepartment of Gastrointestinal Surgery, Helsinki University Hospital, University of Helsinki, Haartmaninkatu 4, FI-00290, Helsinki, Finland.
Laura Renkonen-SinisaloDepartment of Gastrointestinal Surgery, Helsinki University Hospital, University of Helsinki, Haartmaninkatu 4, FI-00290, Helsinki, Finland.
Jukka-Pekka MecklinDepartment of Surgery, Jyväskylä Central Hospital, Keskussairaalantie 19, FI-40620, Jyväskylä, Finland.
Jussi TaipaleGenome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland. ajt208@cam.ac.uk.
Lauri A AaltonenDepartment of Medical and Clinical Genetics, Medicum, University of Helsinki, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014, Helsinki, Finland. lauri.aaltonen@helsinki.fi.
University of Helsinki · FIAarhus University Hospital · DKKarolinska Institutet · SEUniversity of Geneva · CHCentral Finland Health Care District · FI
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
Indexed as
Allelic ImbalanceGenetic Predisposition to DiseaseChromosome AberrationsChromosomes, Human, Pair 8Colorectal NeoplasmsCRISPR-Cas SystemsDenmarkDNA Copy Number VariationsGene Expression ProfilingGenomicsGenotypeHumansLoss of HeterozygosityMicrosatellite RepeatsPhenotypePoint MutationKRAS protein, humanProto-Oncogene Proteins p21(ras)RNA, Small InterferingTP53 protein, humanTranscription FactorsTumor Suppressor Protein p53
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