{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:35:23Z","timestamp":1760142923933,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is the second most common hematological malignancy. Approximately 15% of MM patients are affected by the t(4;14) translocation resulting in the IGH::NSD2 fusion transcript. Breakage occurs in three major breakpoint regions within the NSD2 gene (MB4-1, MB4-2, and MB4-3), where MB4-1 leads to the production of full-length protein, while truncated proteins are expressed in the other two cases. Measurable residual disease (MRD) has been conclusively established as a crucial prognostic factor in MM. The IGH::NSD2 fusion transcript can serve as a sensitive MRD marker. Using bone marrow (BM) and peripheral blood (PB) samples from 111 patients, we developed a highly sensitive quantitative real-time PCR (qPCR) and digital PCR (dPCR) system capable of detecting fusion mRNAs with a sensitivity of up to 1:100,000. PB samples exhibited sensitivity three orders of magnitude lower compared to BM samples. Patients with an MB4-2 breakpoint demonstrated significantly reduced overall survival (p = 0.003). Our novel method offers a simple and sensitive means for detecting MRD in a substantial proportion of MM patients. Monitoring may be carried out even from PB samples. The literature lacks consensus regarding survival outcomes among patients with different NSD2 breakpoints. Our data align with previous findings indicating that patients with the MB4-2 breakpoint type tend to exhibit unfavorable overall survival.<\/jats:p>","DOI":"10.3390\/cancers16020283","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T03:36:58Z","timestamp":1704771418000},"page":"283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IGH::NSD2 Fusion Gene Transcript as Measurable Residual Disease Marker in Multiple Myeloma"],"prefix":"10.3390","volume":"16","author":[{"given":"Andr\u00e1s","family":"Bors","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5075-9953","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Kozma","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4345-9067","authenticated-orcid":false,"given":"\u00c1gnes","family":"Tom\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-2206","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"\u0150rfi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N\u00f3ra","family":"Kondor","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szabolcs","family":"Tasn\u00e1dy","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"V\u00e1lyi-Nagy","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Rem\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-7398","authenticated-orcid":false,"given":"G\u00e1bor","family":"Mikala","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajnalka","family":"Andrikovics","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Central Hospital of Southern Pest-National Institute of Hematology and Infectious Disease, H-1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1038\/s41467-019-11680-1","article-title":"Genomic landscape and chronological reconstruction of driver events in multiple myeloma","volume":"10","author":"Maura","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrc3257","article-title":"The genetic architecture of multiple myeloma","volume":"12","author":"Morgan","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1080\/10428194.2021.1957875","article-title":"Disease heterogeneity, prognostication and the role of targeted therapy in multiple myeloma","volume":"62","author":"Zanwar","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.3324\/haematol.2018.189159","article-title":"European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: What to use and when","volume":"103","author":"Caers","year":"2018","journal-title":"Haematologica"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1001\/jamaoncol.2016.3160","article-title":"Association of Minimal Residual Disease with Superior Survival Outcomes in Patients with Multiple Myeloma: A Meta-analysis","volume":"3","author":"Munshi","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1182\/blood-2018-06-858613","article-title":"Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma","volume":"132","author":"Perrot","year":"2018","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/bjh.15075","article-title":"Molecular detection of minimal residual disease in multiple myeloma","volume":"181","author":"Bai","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3389\/fonc.2019.00699","article-title":"Minimal Residual Disease Assessment within the Bone Marrow of Multiple Myeloma: A Review of Caveats, Clinical Significance and Future Perspectives","volume":"9","author":"Romano","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.3324\/haematol.2011.056176","article-title":"Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders","volume":"97","author":"Ross","year":"2012","journal-title":"Haematologica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1200\/EDBK_175175","article-title":"Established and Novel Prognostic Biomarkers in Multiple Myeloma","volume":"37","author":"Bustoros","year":"2017","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e471","DOI":"10.3324\/haematol.2015.127001","article-title":"MB4-2 breakpoint in MMSET combined with del(17p) defines a subset of t(4;14) multiple myeloma with very poor prognosis","volume":"100","author":"Lazareth","year":"2015","journal-title":"Haematologica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51608","DOI":"10.18632\/oncotarget.18209","article-title":"MB4-2\/MB4-3 transcripts of IGH-MMSET fusion gene in t(4;14)(pos) multiple myeloma indicate poor prognosis","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","first-page":"4058","article-title":"Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by reverse transcription-polymerase chain reaction analysis of IGH-MMSET fusion transcripts","volume":"60","author":"Malgeri","year":"2000","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2141.2006.06479.x","article-title":"Detection and follow-up of fibroblast growth factor receptor 3 expression on bone marrow and circulating plasma cells by flow cytometry in patients with t(4;14) multiple myeloma","volume":"136","author":"Chandesris","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/sj.leu.2403135","article-title":"Standardization and quality control studies of \u2018real-time\u2019 quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia\u2014A Europe Against Cancer program","volume":"17","author":"Gabert","year":"2003","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1200\/JCO.21.02614","article-title":"Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report within the HARMONY Project","volume":"40","author":"Cairns","year":"2022","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gks596","article-title":"Primer3--new capabilities and interfaces","volume":"40","author":"Untergasser","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1038\/sj.leu.2403136","article-title":"Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using \u2018real-time\u2019 quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR)\u2014A Europe against cancer program","volume":"17","author":"Beillard","year":"2003","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1515\/cclm-2015-0869","article-title":"How to assess the quality of your analytical method?","volume":"53","author":"Topic","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"McAvera, R., Quinn, J., Murphy, P., and Glavey, S. (2023). Genetic Abnormalities in Extramedullary Multiple Myeloma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411259"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1182\/blood-2004-09-3704","article-title":"Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients","volume":"105","author":"Keats","year":"2005","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1182\/blood.2022016212","article-title":"The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM","volume":"141","author":"Stong","year":"2023","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/2\/283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:42:38Z","timestamp":1760103758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/2\/283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,9]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cancers16020283"],"URL":"https:\/\/doi.org\/10.3390\/cancers16020283","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2024,1,9]]}}}