{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:25:55Z","timestamp":1787502355785,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T00:00:00Z","timestamp":1688860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extramedullary multiple myeloma (or extramedullary disease, EMD) is an aggressive form of multiple myeloma (MM) that occurs when malignant plasma cells become independent of the bone marrow microenvironment. This may occur alongside MM diagnosis or in later stages of relapse and confers an extremely poor prognosis. In the era of novel agents and anti-myeloma therapies, the incidence of EMD is increasing, making this a more prevalent and challenging cohort of patients. Therefore, understanding the underlying mechanisms of bone marrow escape and EMD driver events is increasingly urgent. The role of genomics in MM has been studied extensively; however, much less is known about the genetic background of EMD. Recently there has been an increased focus on driver events for the establishment of distant EMD sites. Generally, high-risk cytogenetic abnormalities and gene signatures are associated with EMD, alongside mutations in RAS signalling pathways. More recently, changes in epigenetic regulation have also been documented, specifically the hypermethylation of DNA promoter regions. Therefore, the focus of this review is to summarize and discuss what is currently known about the genetic background of EMD in MM.<\/jats:p>","DOI":"10.3390\/ijms241411259","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:35:21Z","timestamp":1688949321000},"page":"11259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Genetic Abnormalities in Extramedullary Multiple Myeloma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1222-3047","authenticated-orcid":false,"given":"Roisin","family":"McAvera","sequence":"first","affiliation":[{"name":"Department of Pathology, Royal College of Surgeons in Ireland, D09 YD60 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Haematology, Beaumont Hospital, D09 V2N0 Dublin, Ireland"},{"name":"School of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Haematology, Beaumont Hospital, D09 V2N0 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8601-2090","authenticated-orcid":false,"given":"Siobhan","family":"Glavey","sequence":"additional","affiliation":[{"name":"Department of Pathology, Royal College of Surgeons in Ireland, D09 YD60 Dublin, Ireland"},{"name":"Department of Haematology, Beaumont Hospital, D09 V2N0 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/ajh.26590","article-title":"Multiple myeloma: 2022 update on diagnosis, risk stratification, and management","volume":"97","author":"Rajkumar","year":"2022","journal-title":"Am. 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