{"entity": "researcher", "timestamp": "2026-08-14T13:27:16.907Z", "family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "affiliations": ["Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund 22185, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff"}}, "publications": [{"entity": "publication", "iuid": "2424a9f7eb5c4b9f85690b0af2c8405e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2424a9f7eb5c4b9f85690b0af2c8405e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2424a9f7eb5c4b9f85690b0af2c8405e"}}, "title": "Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma.", "authors": [{"family": "Karlsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-7681-0059", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2ccecaff1d41bfa863dde6616eeadd.json"}}, {"family": "Yasui", "given": "Hiroaki", "initials": "H"}, {"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}}, {"family": "Hansson", "given": "Karin", "initials": "K", "orcid": "0000-0002-6993-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c0c991068644f61b10c986deff8fb7f.json"}}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Jansson", "given": "Caroline", "initials": "C"}, {"family": "Durand", "given": "Geoffroy", "initials": "G"}, {"family": "Ravi", "given": "Naveen", "initials": "N"}, {"family": "Ferro", "given": "Michele", "initials": "M"}, {"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications.scilifelab.se/researcher/62822d0b9c6c4a01a53829b9b05443ba.json"}}, {"family": "Chattopadhyay", "given": "Subhayan", "initials": "S"}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}, {"family": "Spierings", "given": "Diana", "initials": "D", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F", "orcid": "0000-0003-0989-3127", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ef3e70e2b5249029ff65894fd11b851.json"}}, {"family": "Valind", "given": "Anders", "initials": "A", "orcid": "0000-0002-1654-6978", "researcher": {"href": "https://publications.scilifelab.se/researcher/08f05da015554b19852439d14cb8e99b.json"}}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}], "type": "journal article", "published": "2024-10-18", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "8992", "issn-l": "2041-1723"}, "abstract": "Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicate these two contrasting scenarios and show branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.", "doi": "10.1038/s41467-024-53334-x", "pmid": "39419962", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11486966"}, {"db": "pii", "key": "10.1038/s41467-024-53334-x"}], "notes": [], "created": "2024-11-14T09:28:32.271Z", "modified": "2024-11-17T16:43:33.354Z"}, {"entity": "publication", "iuid": "685ff57e5eac4e2da829fb1497ef3cb0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/685ff57e5eac4e2da829fb1497ef3cb0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/685ff57e5eac4e2da829fb1497ef3cb0"}}, "title": "Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution.", "authors": [{"family": "Rastegar", "given": "Bahar", "initials": "B", "orcid": "0009-0000-8127-9055", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b8a53d89b3e493c9f5181ee697aa224.json"}}, {"family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}}, {"family": "Petersson", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-5574-9217", "researcher": {"href": "https://publications.scilifelab.se/researcher/98f02e97bd25493c993d1a2568935885.json"}}, {"family": "Karlsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-7681-0059", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2ccecaff1d41bfa863dde6616eeadd.json"}}, {"family": "Chattopadhyay", "given": "Subhayan", "initials": "S", "orcid": "0000-0002-8599-2971", "researcher": {"href": "https://publications.scilifelab.se/researcher/78358668578b4661bed1f6a37365fae4.json"}}, {"family": "Valind", "given": "Anders", "initials": "A", "orcid": "0000-0002-1654-6978", "researcher": {"href": "https://publications.scilifelab.se/researcher/08f05da015554b19852439d14cb8e99b.json"}}, {"family": "Jansson", "given": "Caroline", "initials": "C", "orcid": "0009-0001-4115-0414", "researcher": {"href": "https://publications.scilifelab.se/researcher/18d696fca9d64a9f841c0ad59d454156.json"}}, {"family": "Durand", "given": "Geoffroy", "initials": "G", "orcid": "0000-0001-9004-7248", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb5b34538f984b95a79dd581071df344.json"}}, {"family": "Romerius", "given": "Patrik", "initials": "P", "orcid": "0009-0000-4651-4734", "researcher": {"href": "https://publications.scilifelab.se/researcher/62e4a9a4a92448ef8f019ff74390dd7c.json"}}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K", "orcid": "0000-0003-2257-5000", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b7c5c8216d943d2b344d9de5622770b.json"}}, {"family": "Holmquist Mengelbier", "given": "Linda", "initials": "L", "orcid": "0000-0002-3632-2760", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6729b3f10e84432839564c382473607.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}], "type": "journal article", "published": "2023-07-14", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "volume": "29", "issue": "14", "pages": "2668-2677", "issn-l": "1078-0432"}, "abstract": "While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors.\n\nWe spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction. Tumor whole-mount sections (WMS) were utilized to characterize the distribution of subclones across anatomically distinct tumor compartments.\n\nCompared with non-diffuse anaplasia Wilms tumors, tumors with diffuse anaplasia showed a significantly higher number of genetically distinct tumor cell subpopulations and more complex phylogenetic trees, including high levels of phylogenetic species richness, divergence, and irregularity. All regions with classical anaplasia showed TP53 alterations. TP53 mutations were frequently followed by saltatory evolution and parallel loss of the remaining wild-type (WT) allele in different regions. Morphologic features of anaplasia increased with copy-number aberration (CNA) burden and regressive features. Compartments demarcated by fibrous septae or necrosis/regression were frequently (73%) associated with the emergence of new clonal CNAs, although clonal sweeps were rare within these compartments.\n\nWilms tumors with diffuse anaplasia display significantly more complex phylogenies compared with non-diffuse anaplasia Wilms tumors, including features of saltatory and parallel evolution. The subclonal landscape of individual tumors was constrained by anatomic compartments, which should be considered when sampling tissue for precision diagnostics.", "doi": "10.1158/1078-0432.CCR-23-0311", "pmid": "37140929", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10345961"}, {"db": "pii", "key": "726309"}], "notes": [], "created": "2024-01-07T18:18:34.759Z", "modified": "2024-01-07T18:18:35.257Z"}, {"entity": "publication", "iuid": "73b6ae96c1c84230803743ff7ac85552", "links": {"self": {"href": "https://publications.scilifelab.se/publication/73b6ae96c1c84230803743ff7ac85552.json"}, "display": {"href": "https://publications.scilifelab.se/publication/73b6ae96c1c84230803743ff7ac85552"}}, "title": "Inactivation of RB1, CDKN2A, and TP53 have distinct effects on genomic stability at side-by-side comparison in karyotypically normal cells.", "authors": [{"family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}}, {"family": "Saba", "given": "Karim H", "initials": "KH", "orcid": "0000-0003-4946-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/42cc0dd26f394abb9117550f4e5a034c.json"}}, {"family": "Magnusson", "given": "Linda", "initials": "L", "orcid": "0000-0002-4242-3461", "researcher": {"href": "https://publications.scilifelab.se/researcher/63c3ef7e774e41c6aefd376543a6f10a.json"}}, {"family": "Nilsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-5593-3009", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6b1e0ee6f2641619a3692a230d49e00.json"}}, {"family": "Karlsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-7681-0059", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2ccecaff1d41bfa863dde6616eeadd.json"}}, {"family": "Nord", "given": "Karolin H", "initials": "KH", "orcid": "0000-0002-2397-2254", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a3367cdd2a44c23aad89d176be5b74c.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}], "type": "journal article", "published": "2023-02-00", "journal": {"title": "Genes Chromosomes Cancer", "issn": "1098-2264", "volume": "62", "issue": "2", "pages": "93-100", "issn-l": "1045-2257"}, "abstract": "Chromosomal instability is a common feature in malignant tumors. Previous studies have indicated that inactivation of the classical tumor suppressor genes RB1, CDKN2A, and TP53 may contribute to chromosomal aberrations in cancer by disrupting different aspects of the cell cycle and DNA damage checkpoint machinery. We performed a side-by-side comparison of how inactivation of each of these genes affected chromosomal stability in vitro. Using CRISPR-Cas9 technology, RB1, CDKN2A, and TP53 were independently knocked out in karyotypically normal immortalized cells, after which these cells were followed over time. Bulk RNA sequencing revealed a distinct phenotype with upregulation of pathways related to cell cycle control and proliferation in all three knockouts. Surprisingly, the RB1 and CDKN2A knocked out cell lines did not harbor more copy number aberrations than wild-type cells, despite culturing for months. The TP53-knocked out cells, in contrast, showed a massive amount of copy number alterations and saltatory evolution through whole genome duplication. This side-by-side comparison indicated that the effects on chromosomal stability from inactivation of RB1 and CDKN2A are negligible compared to inactivation of TP53, under the same conditions in a nonstressful environment, even though partly overlapping regulatory pathways are affected. Our data suggest that loss of RB1 and CDKN2A alone is not enough to trigger surviving detectable aneuploid clones while inactivation of TP53 on its own caused massive CIN leading to saltatory clonal evolution in vitro and clonal selection.", "doi": "10.1002/gcc.23096", "pmid": "36124964", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2023-02-20T13:56:39.540Z", "modified": "2023-02-20T13:56:39.634Z"}, {"entity": "publication", "iuid": "ed05b16509414bc8b557611000e36d26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed05b16509414bc8b557611000e36d26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed05b16509414bc8b557611000e36d26"}}, "title": "Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance.", "authors": [{"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Andersson", "given": "Natalie", "initials": "N", "orcid": "0000-0002-3643-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7ef3a8564354a78a23180c7550a03ff.json"}}, {"family": "Hansson", "given": "Karin", "initials": "K", "orcid": "0000-0002-6993-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c0c991068644f61b10c986deff8fb7f.json"}}, {"family": "Adamska", "given": "Aleksandra", "initials": "A", "orcid": "0000-0002-7152-4149", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f2fab5686a542fdb1286417685bc7a4.json"}}, {"family": "Seger", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-3191-5302", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfcd0a0a226c417eac8e0a48eedd4e7c.json"}}, {"family": "Yasui", "given": "Hiroaki", "initials": "H"}, {"family": "van den Bos", "given": "Hilda", "initials": "H", "orcid": "0000-0001-9787-8597", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3f0fd58a2714db5bcd89642f92c0158.json"}}, {"family": "Radke", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-4460-0812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad483c946ce244fa898cadb6238e970d.json"}}, {"family": "Esfandyari", "given": "Javanshir", "initials": "J"}, {"family": "Bhave", "given": "Madhura Satish", "initials": "MS"}, {"family": "Karlsson", "given": "Jenny", "initials": "J", "orcid": "0000-0001-7681-0059", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2ccecaff1d41bfa863dde6616eeadd.json"}}, {"family": "Spierings", "given": "Diana", "initials": "D", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F", "orcid": "0000-0003-0989-3127", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ef3e70e2b5249029ff65894fd11b851.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}], "type": "journal article", "published": "2022-10-28", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "8", "issue": "43", "pages": "eabq4617", "issn-l": "2375-2548"}, "abstract": "Chemotherapy resistance and relapses are common in high-risk neuroblastoma (NB). Here, we developed a clinically relevant in vivo treatment protocol mimicking the first-line five-chemotherapy treatment regimen of high-risk NB and applied this protocol to mice with MYCN-amplified NB patient-derived xenografts (PDXs). Genomic and transcriptomic analyses were used to reveal NB chemoresistance mechanisms. Intrinsic resistance was associated with high genetic diversity and an embryonic phenotype. Relapsed NB with acquired resistance showed a decreased adrenergic phenotype and an enhanced immature mesenchymal-like phenotype, resembling multipotent Schwann cell precursors. NBs with a favorable treatment response presented a lineage-committed adrenergic phenotype similar to normal neuroblasts. Novel integrated phenotypic gene signatures reflected treatment response and patient prognosis. NB organoids established from relapsed PDX tumors retained drug resistance, tumorigenicity, and transcriptional cell states. This work sheds light on the mechanisms of NB chemotherapy response and emphasizes the importance of transcriptional cell states in chemoresistance.", "doi": "10.1126/sciadv.abq4617", "pmid": "36306349", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9616506"}], "notes": [], "created": "2022-11-15T12:56:52.046Z", "modified": "2023-06-01T06:43:02.747Z"}]}