{"entity": "researcher", "timestamp": "2026-07-15T16:13:06.517Z", "family": "Spierings", "given": "Diana C J", "initials": "DCJ", "orcid": "0000-0001-8403-474X", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2"}}, "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": "78c6f628dba44764b202cc75c9d2cb2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/78c6f628dba44764b202cc75c9d2cb2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/78c6f628dba44764b202cc75c9d2cb2f"}}, "title": "CDK4 is co-amplified with either TP53 promoter gene fusions or MDM2 through distinct mechanisms in osteosarcoma.", "authors": [{"family": "Saba", "given": "Karim H", "initials": "KH", "orcid": "0000-0003-4946-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/42cc0dd26f394abb9117550f4e5a034c.json"}}, {"family": "Difilippo", "given": "Valeria", "initials": "V", "orcid": "0000-0002-5965-942X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e727c9e72f5499ea1993647fc739d6e.json"}}, {"family": "Styring", "given": "Emelie", "initials": "E"}, {"family": "Nilsson", "given": "Jenny", "initials": "J"}, {"family": "Magnusson", "given": "Linda", "initials": "L"}, {"family": "van den Bos", "given": "Hilda", "initials": "H"}, {"family": "Wardenaar", "given": "Ren\u00e9", "initials": "R", "orcid": "0000-0001-9891-1897", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb1c5b299299417b807addb300a87ba4.json"}}, {"family": "Spierings", "given": "Diana C J", "initials": "DCJ", "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": "Nathrath", "given": "Michaela", "initials": "M", "orcid": "0000-0002-1584-1115", "researcher": {"href": "https://publications.scilifelab.se/researcher/856d90d57b574a289b4b886a44ca3af1.json"}}, {"family": "Haglund de Flon", "given": "Felix", "initials": "F", "orcid": "0000-0002-7015-3841", "researcher": {"href": "https://publications.scilifelab.se/researcher/891cbee146fa4e27bc8d26111283b854.json"}}, {"family": "Baumhoer", "given": "Daniel", "initials": "D", "orcid": "0000-0002-2137-7507", "researcher": {"href": "https://publications.scilifelab.se/researcher/309ba2d6eec34bbe8862e62e2ea401b6.json"}}, {"family": "Nord", "given": "Karolin H", "initials": "KH", "orcid": "0000-0002-2397-2254", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a3367cdd2a44c23aad89d176be5b74c.json"}}], "type": "journal article", "published": "2024-09-25", "journal": {"title": "npj Genom. Med.", "issn": "2056-7944", "volume": "9", "issue": "1", "pages": "42", "issn-l": "2056-7944"}, "abstract": "Amplification of the MDM2 and CDK4 genes on chromosome 12 is commonly associated with low-grade osteosarcomas. In this study, we conducted high-resolution genomic and transcriptomic analyses on 33 samples from 25 osteosarcomas, encompassing both high- and low-grade cases with MDM2 and/or CDK4 amplification. We discerned four major subgroups, ranging from nearly intact genomes to heavily rearranged ones, each harbouring CDK4 and MDM2 amplification or CDK4 amplification with TP53 structural alterations. While amplicons involving MDM2 exhibited signs of an initial chromothripsis event, no evidence of chromothripsis was found in TP53-rearranged cases. Instead, the initial disruption of the TP53 locus led to co-amplification of the CDK4 locus. Additionally, we observed recurring promoter swapping events involving the regulatory regions of the FRS2, PLEKHA5, and TP53 genes. These events resulted in ectopic expression of partner genes, with the ELF1 gene being upregulated by the FRS2 and TP53 promoter regions in two distinct cases.", "doi": "10.1038/s41525-024-00430-y", "pmid": "39322633", "labels": {"NGI Long read": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11424644"}, {"db": "pii", "key": "10.1038/s41525-024-00430-y"}], "notes": [], "created": "2024-10-08T11:20:05.326Z", "modified": "2025-02-28T14:15:07.931Z"}, {"entity": "publication", "iuid": "8c7130dfb41048cfab1512c157df9c8f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8c7130dfb41048cfab1512c157df9c8f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8c7130dfb41048cfab1512c157df9c8f"}}, "title": "MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma.", "authors": [{"family": "Sydow", "given": "Saskia", "initials": "S", "orcid": "0009-0003-0358-8268", "researcher": {"href": "https://publications.scilifelab.se/researcher/549dec30972c44d89378c04fc5f57aa1.json"}}, {"family": "Piccinelli", "given": "Paul", "initials": "P"}, {"family": "Mitra", "given": "Shamik", "initials": "S", "orcid": "0000-0001-6995-0600", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3b10a7bd10941d58ee17b74795931fd.json"}}, {"family": "Tsagkozis", "given": "Panagiotis", "initials": "P"}, {"family": "Hesla", "given": "Asle", "initials": "A", "orcid": "0000-0001-6205-0773", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c3368bd0fa243eea704f1163a815caa.json"}}, {"family": "B R De Mattos", "given": "Camila", "initials": "C", "orcid": "0000-0002-5698-6281", "researcher": {"href": "https://publications.scilifelab.se/researcher/b21c8d7c09424208984c0f16c66e1a82.json"}}, {"family": "K\u00f6ster", "given": "Jan", "initials": "J"}, {"family": "Magnusson", "given": "Linda", "initials": "L"}, {"family": "Nilsson", "given": "Jenny", "initials": "J"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Wardenaar", "given": "Ren\u00e9", "initials": "R", "orcid": "0000-0001-9891-1897", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb1c5b299299417b807addb300a87ba4.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F", "orcid": "0000-0003-0989-3127", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ef3e70e2b5249029ff65894fd11b851.json"}}, {"family": "Spierings", "given": "Diana", "initials": "D", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Mertens", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-6278-5232", "researcher": {"href": "https://publications.scilifelab.se/researcher/909230c16f7840a49798794167232e76.json"}}], "type": "journal article", "published": "2024-05-20", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "7", "issue": "1", "pages": "606", "issn-l": "2399-3642"}, "abstract": "Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.", "doi": "10.1038/s42003-024-06307-1", "pmid": "38769442", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11106292"}, {"db": "pii", "key": "10.1038/s42003-024-06307-1"}], "notes": [], "created": "2024-08-02T12:15:20.754Z", "modified": "2024-11-14T09:20:12.214Z"}, {"entity": "publication", "iuid": "8c62fc49e69343088f6622db30a0504a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8c62fc49e69343088f6622db30a0504a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8c62fc49e69343088f6622db30a0504a"}}, "title": "Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia.", "authors": [{"family": "Woodward", "given": "Eleanor L", "initials": "EL"}, {"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications.scilifelab.se/researcher/62822d0b9c6c4a01a53829b9b05443ba.json"}}, {"family": "Moura-Castro", "given": "Larissa H", "initials": "LH", "orcid": "0000-0001-9063-5592", "researcher": {"href": "https://publications.scilifelab.se/researcher/d326f608c7744622a92cc73768f23afb.json"}}, {"family": "van den Bos", "given": "Hilda", "initials": "H"}, {"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Olsson-Arvidsson", "given": "Linda", "initials": "L"}, {"family": "Spierings", "given": "Diana C J", "initials": "DCJ", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Castor", "given": "Anders", "initials": "A"}, {"family": "Duployez", "given": "Nicolas", "initials": "N"}, {"family": "Zaliova", "given": "Marketa", "initials": "M", "orcid": "0000-0002-1639-7124", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc439d4e47984c11a566df2d4e1a1dcd.json"}}, {"family": "Zuna", "given": "Jan", "initials": "J", "orcid": "0000-0002-0887-3709", "researcher": {"href": "https://publications.scilifelab.se/researcher/34c778d142f84ee3add0199b823ed356.json"}}, {"family": "Johansson", "given": "Bertil", "initials": "B", "orcid": "0000-0001-8829-4813", "researcher": {"href": "https://publications.scilifelab.se/researcher/fed657adae7f49f2b8d052cff36eac07.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F", "orcid": "0000-0003-0989-3127", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ef3e70e2b5249029ff65894fd11b851.json"}}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}], "type": "journal article", "published": "2023-03-25", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "1658", "issn-l": "2041-1723"}, "abstract": "High hyperdiploid acute lymphoblastic leukemia (HeH ALL), one of the most common childhood malignancies, is driven by nonrandom aneuploidy (abnormal chromosome numbers) mainly comprising chromosomal gains. In this study, we investigate how aneuploidy in HeH ALL arises. Single cell whole genome sequencing of 2847 cells from nine primary cases and one normal bone marrow reveals that HeH ALL generally display low chromosomal heterogeneity, indicating that they are not characterized by chromosomal instability and showing that aneuploidy-driven malignancies are not necessarily chromosomally heterogeneous. Furthermore, most chromosomal gains are present in all leukemic cells, suggesting that they arose early during leukemogenesis. Copy number data from 577 primary cases reveals selective pressures that were used for in silico modeling of aneuploidy development. This shows that the aneuploidy in HeH ALL likely arises by an initial tripolar mitosis in a diploid cell followed by clonal evolution, in line with a punctuated evolution model.", "doi": "10.1038/s41467-023-37356-5", "pmid": "36966135", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10039905"}, {"db": "pii", "key": "10.1038/s41467-023-37356-5"}], "notes": [], "created": "2024-01-07T09:05:55.224Z", "modified": "2024-01-07T09:05:55.466Z"}, {"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"}, {"entity": "publication", "iuid": "c415e1ad145e4e3980e7a96e3c492895", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c415e1ad145e4e3980e7a96e3c492895.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c415e1ad145e4e3980e7a96e3c492895"}}, "title": "Extensive Clonal Branching Shapes the Evolutionary History of High-Risk Pediatric Cancers.", "authors": [{"family": "Andersson", "given": "Natalie", "initials": "N"}, {"family": "Bakker", "given": "Bjorn", "initials": "B", "orcid": "0000-0003-3095-7287", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2f6637d70ea487bbd752150140416dc.json"}}, {"family": "Karlsson", "given": "Jenny", "initials": "J"}, {"family": "Valind", "given": "Anders", "initials": "A"}, {"family": "Holmquist Mengelbier", "given": "Linda", "initials": "L", "orcid": "0000-0002-3632-2760", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6729b3f10e84432839564c382473607.json"}}, {"family": "Spierings", "given": "Diana C J", "initials": "DCJ", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F"}, {"family": "Gisselsson", "given": "David", "initials": "D"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "7", "pages": "1512-1523", "issn-l": "0008-5472"}, "abstract": "Darwinian evolution of tumor cells remains underexplored in childhood cancer. We here reconstruct the evolutionary histories of 56 pediatric primary tumors, including 24 neuroblastomas, 24 Wilms tumors, and 8 rhabdomyosarcomas. Whole-genome copy-number and whole-exome mutational profiling of multiple regions per tumor were performed, followed by clonal deconvolution to reconstruct a phylogenetic tree for each tumor. Overall, 88% of the tumors exhibited genetic variation among primary tumor regions. This variability typically emerged through collateral phylogenetic branching, leading to spatial variability in the distribution of more than 50% (96/173) of detected diagnostically informative genetic aberrations. Single-cell sequencing of 547 individual cancer cells from eight solid pediatric tumors confirmed branching evolution to be a fundamental underlying principle of genetic variation in all cases. Strikingly, cell-to-cell genetic diversity was almost twice as high in aggressive compared with clinically favorable tumors (median Simpson index of diversity 0.45 vs. 0.88; P = 0.029). Similarly, a comparison of multiregional sampling data from a total of 274 tumor regions showed that new phylogenetic branches emerge at a higher frequency per sample and carry a higher mutational load in high-risk than in low-risk tumors. Timelines based on spatial genetic variation showed that the mutations most influencing relapse risk occur at initiation of clonal expansion in neuroblastoma and rhabdomyosarcoma, whereas in Wilms tumor, they are late events. Thus, from an evolutionary standpoint, some high-risk childhood cancers are born bad, whereas others grow worse over time. SIGNIFICANCE: Different pediatric cancers with a high risk of relapse share a common generic pattern of extensively branching evolution of somatic mutations. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/7/1512/F1.large.jpg.", "doi": "10.1158/0008-5472.CAN-19-3468", "pmid": "32041836", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-3468"}], "notes": [], "created": "2020-07-08T13:05:37.152Z", "modified": "2021-11-10T12:52:26.783Z"}]}