{"entity": "researcher", "timestamp": "2026-07-20T21:49:39.841Z", "family": "Merino", "given": "Lara G", "initials": "LG", "orcid": "0000-0002-7208-953X", "affiliations": ["Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Science for Life Laboratory, 171 65, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e989808f60c4a60861c99df3ec9ac25.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e989808f60c4a60861c99df3ec9ac25"}}, "publications": [{"entity": "publication", "iuid": "83f1b92c995e4520a99d0cdc9a6aa254", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/83f1b92c995e4520a99d0cdc9a6aa254.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/83f1b92c995e4520a99d0cdc9a6aa254"}}, "title": "Intrinsic deletion at 10q23.31, including the PTEN gene locus, is aggravated upon CRISPR-Cas9-mediated genome engineering in HAP1 cells mimicking cancer profiles.", "authors": [{"family": "Geng", "given": "Keyi", "initials": "K", "orcid": "0000-0003-0892-7460", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a56ac387ab324409b2c0dc24b9be5d73.json"}}, {"family": "Merino", "given": "Lara G", "initials": "LG", "orcid": "0000-0002-7208-953X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e989808f60c4a60861c99df3ec9ac25.json"}}, {"family": "Veiga", "given": "Ra\u00fcl G", "initials": "RG", "orcid": "0000-0002-8517-1559", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83061a12fa3045d1a878a092a19acc20.json"}}, {"family": "Sommerauer", "given": "Christian", "initials": "C", "orcid": "0000-0001-7132-7172", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1fdc4a7e8f774940b9982c40ead59c30.json"}}, {"family": "Epperlein", "given": "Janine", "initials": "J", "orcid": "0000-0002-1595-5411", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7893c5b8b764a568bc18d540bafb571.json"}}, {"family": "Brinkman", "given": "Eva K", "initials": "EK", "orcid": "0000-0003-3120-1174", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3b448eca9f6345dc85473c7fc71bb1b2.json"}}, {"family": "Kutter", "given": "Claudia", "initials": "C", "orcid": "0000-0002-8047-0058", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a4c9dcde56304ab2a99bb1032e4ce834.json"}}], "type": "journal article", "published": "2024-02-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "volume": "7", "issue": "2", "issn-l": null}, "abstract": "The CRISPR-Cas9 system is a powerful tool for studying gene functions and holds potential for disease treatment. However, precise genome editing requires thorough assessments to minimize unintended on- and off-target effects. Here, we report an unexpected 283-kb deletion on Chromosome 10 (10q23.31) in chronic myelogenous leukemia-derived HAP1 cells, which are frequently used in CRISPR screens. The deleted region encodes regulatory genes, including PAPSS2, ATAD1, KLLN, and PTEN We found that this deletion was not a direct consequence of CRISPR-Cas9 off-targeting but rather occurred frequently during the generation of CRISPR-Cas9-modified cells. The deletion was associated with global changes in histone acetylation and gene expression, affecting fundamental cellular processes such as cell cycle and DNA replication. We detected this deletion in cancer patient genomes. As in HAP1 cells, the deletion contributed to similar gene expression patterns among cancer patients despite interindividual differences. Our findings suggest that the unintended deletion of 10q23.31 can confound CRISPR-Cas9 studies and underscore the importance to assess unintended genomic changes in CRISPR-Cas9-modified cells, which could impact cancer research.", "doi": "10.26508/lsa.202302128", "pmid": "37984988", "labels": {"Claudia Kutter": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "7/2/e202302128"}], "notes": [], "created": "2023-11-21T20:24:17.121Z", "modified": "2023-11-21T20:29:30.111Z"}, {"entity": "publication", "iuid": "3246388c1b374028b463127a62ced10f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3246388c1b374028b463127a62ced10f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3246388c1b374028b463127a62ced10f"}}, "title": "CRISPR-Cas9-mediated genome engineering exaggerates genomic deletion at 10q23.31 including the<i>PTEN<\/i>gene locus mimicking cancer profiles", "authors": [{"family": "Geng", "given": "Keyi", "initials": "K", "orcid": "0000-0003-0892-7460", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a56ac387ab324409b2c0dc24b9be5d73.json"}}, {"family": "Merino", "given": "Lara G", "initials": "LG", "orcid": "0000-0002-7208-953X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e989808f60c4a60861c99df3ec9ac25.json"}}, {"family": "Veiga", "given": "Ra\u00fcl G", "initials": "RG", "orcid": "0000-0002-8517-1559", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83061a12fa3045d1a878a092a19acc20.json"}}, {"family": "Sommerauer", "given": "Christian", "initials": "C", "orcid": "0000-0001-7132-7172", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1fdc4a7e8f774940b9982c40ead59c30.json"}}, {"family": "Epperlein", "given": "Janine", "initials": "J", "orcid": "0000-0002-1595-5411", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7893c5b8b764a568bc18d540bafb571.json"}}, {"family": "Brinkman", "given": "Eva K", "initials": "EK", "orcid": "0000-0003-3120-1174", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3b448eca9f6345dc85473c7fc71bb1b2.json"}}, {"family": "Kutter", "given": "Claudia", "initials": "C", "orcid": "0000-0002-8047-0058", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a4c9dcde56304ab2a99bb1032e4ce834.json"}}], "type": "posted-content", "published": "2023-04-06", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2023.04.05.535680", "pmid": null, "labels": {"SciLifeLab Fellow": null, "Claudia Kutter": null}, "xrefs": [], "notes": [], "created": "2023-05-12T15:53:18.458Z", "modified": "2023-07-04T12:14:43.066Z"}, {"entity": "publication", "iuid": "f5f0ff606e2a4674a4f16cdfe99c6a19", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f5f0ff606e2a4674a4f16cdfe99c6a19.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f5f0ff606e2a4674a4f16cdfe99c6a19"}}, "title": "Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.", "authors": [{"family": "Geng", "given": "Keyi", "initials": "K", "orcid": "0000-0003-0892-7460", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a56ac387ab324409b2c0dc24b9be5d73.json"}}, {"family": "Merino", "given": "Lara G", "initials": "LG", "orcid": "0000-0002-7208-953X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e989808f60c4a60861c99df3ec9ac25.json"}}, {"family": "Wedemann", "given": "Linda", "initials": "L", "orcid": "0000-0003-1096-9037", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed2d03a9efe42838005d02101aa1591.json"}}, {"family": "Martens", "given": "Aniek", "initials": "A", "orcid": "0000-0002-0291-0281", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9fa7441c1f24c4689fa884748cb1722.json"}}, {"family": "Sobota", "given": "Ma\u0142gorzata", "initials": "M"}, {"family": "Sanchez", "given": "Yerma P", "initials": "YP", "orcid": "0000-0003-2008-5390", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c66abc222f14d7b80591307113af56e.json"}}, {"family": "S\u00f8ndergaard", "given": "Jonas N\u00f8rskov", "initials": "JN", "orcid": "0000-0002-4438-6756", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85be14546c6e4c28a3171880521ed29c.json"}}, {"family": "White", "given": "Robert J", "initials": "RJ", "orcid": "0000-0002-9631-7760", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a36167f04c94e29a973b9155083e6d9.json"}}, {"family": "Kutter", "given": "Claudia", "initials": "C", "orcid": "0000-0002-8047-0058", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a4c9dcde56304ab2a99bb1032e4ce834.json"}}], "type": "journal article", "published": "2022-10-00", "journal": {"title": "Genome Res", "issn": "1549-5469", "volume": "32", "issue": "10", "pages": "1876-1891", "issn-l": "1088-9051"}, "abstract": "The CRISPR-Cas9 system is widely used to permanently delete genomic regions via dual guide RNAs. Genomic rearrangements induced by CRISPR-Cas9 can occur, but continuous technical developments make it possible to characterize complex on-target effects. We combined an innovative droplet-based target enrichment approach with long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving the allelic co-occurrence of a genomic duplication and inversion of the target region, as well as integrations of exogenous DNA and clustered interchromosomal DNA fragment rearrangements. Furthermore, we found that these genomic alterations led to functional aberrant DNA fragments and can alter cell proliferation. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations, and introduce a data-driven workflow enabling detailed dissection of the on-target sequence content with superior resolution.", "doi": "10.1101/gr.276901.122", "pmid": "36180232", "labels": {"SciLifeLab Fellow": null, "Claudia Kutter": null}, "xrefs": [{"db": "pii", "key": "gr.276901.122"}], "notes": [], "created": "2022-11-28T11:18:35.200Z", "modified": "2022-11-28T11:18:35.507Z"}]}