{"entity": "researcher", "timestamp": "2026-09-28T11:19:30.034Z", "family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "affiliations": ["Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, SE-221 84, Lund, Sweden. kajsa.paulsson@med.lu.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/54d7266ff8fc4ba98245c1ec0d99df65.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/54d7266ff8fc4ba98245c1ec0d99df65"}}, "publications": [{"entity": "publication", "iuid": "de4cd2a7d84b48a2b3360119956ee3f7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/de4cd2a7d84b48a2b3360119956ee3f7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/de4cd2a7d84b48a2b3360119956ee3f7"}}, "title": "Discovery of Cis-Regulatory Mechanisms via Non-Coding Mutations in Acute Lymphoblastic Leukemia.", "authors": [{"family": "Ayd\u0131n", "given": "Efe", "initials": "E"}, {"family": "Woodward", "given": "Eleanor L", "initials": "EL"}, {"family": "Dushime", "given": "Gladys Telliam", "initials": "GT"}, {"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83d3c8e64bb5452a9a6332c0a21a5a51.json"}}, {"family": "Moura-Castro", "given": "Larissa H", "initials": "LH", "orcid": "0000-0001-9063-5592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c179e6300854e2eba9a7bfc0556a1f9.json"}}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Johansson", "given": "Bertil", "initials": "B"}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54d7266ff8fc4ba98245c1ec0d99df65.json"}}, {"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/820e5a34c12f41458487bba712d486ed.json"}}], "type": "journal article", "published": "2025-03-00", "journal": {"title": "Genes Chromosomes Cancer", "issn": "1098-2264", "volume": "64", "issue": "3", "pages": "e70045", "issn-l": "1045-2257"}, "abstract": "The non-coding genome, constituting 98% of human DNA, remains largely unexplored, yet holds potential for identifying new biomarkers and therapeutic targets in acute lymphoblastic leukemia (ALL). In this study, we conducted a systematic analysis of recurrent somatic non-coding single nucleotide variants (SNVs) in pediatric B-cell precursor (BCP) ALL. We leveraged whole genome sequencing (WGS) data from 345 pediatric BCP ALL cases, representing all major genetic subtypes and identified 346 mutational hotspots that harbored somatic SNVs in at least three cases. Through the integration of paired RNA sequencing along with published ChIP-seq and ATAC-seq data, we found 128 non-coding hotspots associated with differentially expressed genes nearby, which were enriched for cis-regulatory elements, demonstrating the effectiveness of multi-omics integration in distinguishing pathogenic mutations from passengers. We identified one mutational hotspot that was associated with increased expression of the leukemia-associated gene NRAS in three primary ALLs. Micro-C analysis in the leukemia cell line demonstrated interactions between the hotspot region and NRAS regulatory elements. Dual luciferase assays indicated that the mutations disrupted regulatory interactions and CRISPR-mediated deletion of the region significantly upregulated NRAS, confirming the hypothesized regulatory link. Altogether, we provide new insights into the functional roles of non-coding mutations in leukemia.", "doi": "10.1002/gcc.70045", "pmid": "40145864", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11949094"}], "notes": [], "created": "2026-09-23T15:46:40.976Z", "modified": "2026-09-23T15:46:41.084Z"}, {"entity": "publication", "iuid": "8f9e42d6661e4aaa91aa58e60cde36d9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8f9e42d6661e4aaa91aa58e60cde36d9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8f9e42d6661e4aaa91aa58e60cde36d9"}}, "title": "Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia.", "authors": [{"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/820e5a34c12f41458487bba712d486ed.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e443cdb01cc44a7fa786941b5c0b62d6.json"}}, {"family": "Siavelis", "given": "Ioannis", "initials": "I"}, {"family": "Moura-Castro", "given": "Larissa H", "initials": "LH"}, {"family": "Castor", "given": "Anders", "initials": "A"}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95546f158dde40709fbfbb822a8f89c5.json"}}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83d3c8e64bb5452a9a6332c0a21a5a51.json"}}, {"family": "Odom", "given": "Duncan T", "initials": "DT", "orcid": "0000-0001-6201-5599", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8063d3396284b448f03300415fbdb9e.json"}}, {"family": "Olsson", "given": "Linda", "initials": "L"}, {"family": "Ravi", "given": "Naveen", "initials": "N"}, {"family": "Woodward", "given": "Eleanor L", "initials": "EL"}, {"family": "Harewood", "given": "Louise", "initials": "L"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/561efcf32e2648c8a10fee692fc4e908.json"}}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54d7266ff8fc4ba98245c1ec0d99df65.json"}}], "type": "journal article", "published": "2019-04-03", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "10", "issue": "1", "pages": "1519", "issn-l": "2041-1723"}, "abstract": "Hyperdiploidy, i.e. gain of whole chromosomes, is one of the most common genetic features of childhood acute lymphoblastic leukemia (ALL), but its pathogenetic impact is poorly understood. Here, we report a proteogenomic analysis on matched datasets from genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of >8,000 genes and proteins as well as Hi-C of primary patient samples from hyperdiploid and ETV6/RUNX1-positive pediatric ALL. We show that CTCF and cohesin, which are master regulators of chromatin architecture, display low expression in hyperdiploid ALL. In line with this, a general genome-wide dysregulation of gene expression in relation to topologically associating domain (TAD) borders were seen in the hyperdiploid group. Furthermore, Hi-C of a limited number of hyperdiploid childhood ALL cases revealed that 2/4 cases displayed a clear loss of TAD boundary strength and 3/4 showed reduced insulation at TAD borders, with putative leukemogenic effects.", "doi": "10.1038/s41467-019-09469-3", "pmid": "30944321", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6447538"}, {"db": "pii", "key": "10.1038/s41467-019-09469-3"}], "notes": [], "created": "2026-09-23T07:40:50.850Z", "modified": "2026-09-23T07:40:51.024Z"}, {"entity": "publication", "iuid": "2daca50176a84ba4a38dab5246d59692", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2daca50176a84ba4a38dab5246d59692.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2daca50176a84ba4a38dab5246d59692"}}, "title": "Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia.", "authors": [{"family": "Gunnarsson", "given": "Rebeqa", "initials": "R"}, {"family": "Dilorenzo", "given": "Sebastian", "initials": "S"}, {"family": "Lundin-Str\u00f6m", "given": "Kristina B", "initials": "KB"}, {"family": "Olsson", "given": "Linda", "initials": "L"}, {"family": "Biloglav", "given": "Andrea", "initials": "A"}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83d3c8e64bb5452a9a6332c0a21a5a51.json"}}, {"family": "Rissler", "given": "Marianne", "initials": "M"}, {"family": "Wahlberg", "given": "Per", "initials": "P"}, {"family": "Lundmark", "given": "Anders", "initials": "A"}, {"family": "Castor", "given": "Anders", "initials": "A"}, {"family": "Behrendtz", "given": "Mikael", "initials": "M"}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54d7266ff8fc4ba98245c1ec0d99df65.json"}}, {"family": "Isaksson", "given": "Anders", "initials": "A", "orcid": "0000-0001-6576-7825", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/aad89c431f5241f18c0c4173e0a4bce6.json"}}, {"family": "Johansson", "given": "Bertil", "initials": "B"}], "type": "journal article", "published": "2018-10-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "32", "issue": "10", "pages": "2117-2125", "issn-l": "0887-6924"}, "abstract": "High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.", "doi": "10.1038/s41375-018-0092-2", "pmid": "29626196", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6170391"}, {"db": "pii", "key": "10.1038/s41375-018-0092-2"}], "notes": [], "created": "2026-09-23T13:27:18.389Z", "modified": "2026-09-23T13:27:18.471Z"}]}