{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:00:49Z","timestamp":1790226049849,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical College of Wisconsin Cancer Center","id":[{"id":"https:\/\/ror.org\/0115fxs14","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0115fxs14","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society Institutional Research Grant","doi-asserted-by":"publisher","award":["IRG-19-138-34"],"award-info":[{"award-number":["IRG-19-138-34"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"award":["IRG-19-138-34"],"award-info":[{"award-number":["IRG-19-138-34"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Heart, Lung, and Blood Institute","award":["K01HL164972"],"award-info":[{"award-number":["K01HL164972"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"award":["K01HL164972"],"award-info":[{"award-number":["K01HL164972"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K01AG065485"],"award-info":[{"award-number":["K01AG065485"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"award":["K01AG065485"],"award-info":[{"award-number":["K01AG065485"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Blood Cancer United Translational Research Program","award":["6701-25"],"award-info":[{"award-number":["6701-25"]}],"id":[{"id":"https:\/\/ror.org\/0055acf80","id-type":"ROR","asserted-by":"crossref"}]},{"name":"William G. Schuett, Jr. Multiple Myeloma Research Endowment"},{"name":"Riney Family Multiple Myeloma Research Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Individuals of African ancestry (AA) have approximately twofold higher risk of multiple myeloma (MM) than individuals of European ancestry, yet the molecular determinants between monoclonal gammopathy of undetermined significance (MGUS) and MM remain poorly defined. We performed whole-exome sequencing (WES) and genome-wide DNA methylation profiling in 28 AA patients with MM and 28 frequency-matched AA patients with MGUS without documented progression. After quality control, the WES analysis included 28 patients with MGUS and 27 with MM, while the DNA methylation analysis included 27 patients with MGUS and 26 with MM. Whole-exome sequencing identified differences in observed germline variant distributions, with qualifying COL19A1 variants observed only in MGUS and qualifying VWA5B2 variants observed only in MM within this cohort. Gene-burden analyses identified nominal exploratory signals in LAMA5 and PIEZO1, although neither remained significant after Bonferroni correction. DNA methylation profiling identified 703 differentially methylated positions and 122 exploratory candidate differentially methylated regions between MM and MGUS. One 395 bp region spanning 16 CpG sites within RNF39 met the FWER significance threshold. Exploratory pathway analyses implicated oncogenic signaling, cellular stress responses, and cell-death pathways. Although epigenetic age acceleration did not differ between groups, lower DNA methylation (DNAm)-estimated telomere length was observed in MM than in MGUS; however, this difference was borderline after adjustment for DNAm-estimated blood-cell composition. Together these exploratory findings identify germline and epigenetic features associated with MM versus MGUS in AA patients and nominate biological pathways for validation in larger, longitudinal studies.<\/jats:p>","DOI":"10.3390\/cells15191722","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:04:17Z","timestamp":1790067857000},"page":"1722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Germline Genomic and DNA Methylation Differences Between MGUS and Multiple Myeloma Among Patients of African Ancestry"],"prefix":"10.3390","volume":"15","author":[{"given":"Jing","family":"Han","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, USA"},{"name":"Department of Science & Technology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3604-3238","authenticated-orcid":false,"given":"Sophie Hongfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Arsang-Jang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-8902","authenticated-orcid":false,"given":"Zongli","family":"Xu","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Rentscher","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Medical College of Wisconsin Cancer Center, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6763-2710","authenticated-orcid":false,"given":"Angela J.","family":"Mathison","sequence":"additional","affiliation":[{"name":"Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Division of Research, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Tschannen","sequence":"additional","affiliation":[{"name":"Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumou","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Auer","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Data Science Institute, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-0011","authenticated-orcid":false,"given":"Sarah","family":"Kerns","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin Cancer Center, Milwaukee, WI 53226, USA"},{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Hari","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binod","family":"Dhakal","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, 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Milwaukee, WI 53226, USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"D\u2019souza","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-5963","authenticated-orcid":false,"given":"Jing","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, HRC 5860, Milwaukee, WI 53226, USA"},{"name":"Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Medical College of Wisconsin Cancer Center, Milwaukee, WI 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