دورية أكاديمية
أعرض في EDS

Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance.

التفاصيل البيبلوغرافية
العنوان: Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance.
المؤلفون: Thomsen H; MSB Medical School Berlin, Hochschule für Gesundheit und Medizin, Berlin, Germany., Chattopadhyay S; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Weinhold N; Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany., Vodicka P; Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic.; Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Pilsen, Czech Republic., Vodickova L; Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic.; Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Pilsen, Czech Republic., Hoffmann P; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Biomedicine, University of Basel, Basel, Switzerland., Nöthen MM; Institute of Human Genetics, University of Bonn, Bonn, Germany., Jöckel KH; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Schmidt B; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Hajek R; Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic., Hallmans G; Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden., Pettersson-Kymmer U; Clinical Pharmacology, Department of Pharmacology and Clinical Neuroscience, Umea University, Umea, Sweden., Späth F; Department of Diagnostics and Intervention, Cancer Center, Hematology, Umeå University, Umeå, Sweden., Goldschmidt H; Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.; National Centre of Tumor Diseases, Heidelberg, Germany., Hemminki K; Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Pilsen, Czech Republic.; Department of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany., Försti A; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany. a.foersti@kitz-heidelberg.de.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. a.foersti@kitz-heidelberg.de.
المصدر: Blood cancer journal [Blood Cancer J] 2024 Aug 20; Vol. 14 (1), pp. 140. Date of Electronic Publication: 2024 Aug 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101568469 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-5385 (Electronic) Linking ISSN: 20445385 NLM ISO Abbreviation: Blood Cancer J Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Group
مواضيع طبية MeSH: Monoclonal Gammopathy of Undetermined Significance*/genetics , Haplotypes* , Genome-Wide Association Study* , Polymorphism, Single Nucleotide* , Genetic Predisposition to Disease*, Humans ; Male ; Female ; Multiple Myeloma/genetics
مستخلص: Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10 -8 ) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.
(© 2024. The Author(s).)
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تواريخ الأحداث: Date Created: 20240820 Date Completed: 20240820 Latest Revision: 20240823
رمز التحديث: 20240823
مُعرف محوري في PubMed: PMC11335940
DOI: 10.1038/s41408-024-01121-8
PMID: 39164264
قاعدة البيانات: MEDLINE
الوصف
تدمد:2044-5385
DOI:10.1038/s41408-024-01121-8