{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:29:31Z","timestamp":1783960171158,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"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>The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory\/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.<\/jats:p>","DOI":"10.3390\/cancers15235690","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T13:45:41Z","timestamp":1701524741000},"page":"5690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Guilin","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5305-6337","authenticated-orcid":false,"given":"Gokce A.","family":"Toruner","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-3814","authenticated-orcid":false,"given":"Shimin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-0523","authenticated-orcid":false,"given":"Shaoying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzaffar H.","family":"Qazilbash","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-4129","authenticated-orcid":false,"given":"Robert Z.","family":"Orlowski","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Nahmod","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-8006","authenticated-orcid":false,"given":"L. Jeffrey","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-9945","authenticated-orcid":false,"given":"Zhenya","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5412","DOI":"10.1182\/blood-2008-12-194241","article-title":"Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: A prospective study","volume":"113","author":"Landgren","year":"2009","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1182\/blood-2008-12-195008","article-title":"A monoclonal gammopathy precedes multiple myeloma in most patients","volume":"113","author":"Weiss","year":"2009","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1182\/blood-2003-03-0801","article-title":"Long-term follow-up of IgM monoclonal gammopathy of undetermined significance","volume":"102","author":"Kyle","year":"2003","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1056\/NEJMoa070389","article-title":"Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma","volume":"356","author":"Kyle","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1038\/leu.2013.86","article-title":"Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma","volume":"27","author":"Rajkumar","year":"2013","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1200\/JCO.2012.48.4923","article-title":"Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load","volume":"31","author":"Neben","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1038\/s41375-018-0030-3","article-title":"Prognostic significance of interphase FISH in monoclonal gammopathy of undetermined significance","volume":"32","author":"Lakshman","year":"2018","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1200\/JCO.2005.04.242","article-title":"International staging system for multiple myeloma","volume":"23","author":"Greipp","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_9","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."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.mayocp.2013.01.019","article-title":"Management of newly diagnosed symptomatic multiple myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013","volume":"88","author":"Mikhael","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/ajh.26391","article-title":"Prognostic significance of acquired 1q22 gain in multiple myeloma","volume":"97","author":"Audil","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1080\/10428194.2016.1272684","article-title":"Chromosome 1 amplification has similar prognostic value to del(17p13) and t(4;14)(p16;q32) in multiple myeloma patients: Analysis of real-life data from the Polish Myeloma Study Group","volume":"58","author":"Grzasko","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/10245330512331390140","article-title":"Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma","volume":"10","author":"Shaughnessy","year":"2005","journal-title":"Hematology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22","DOI":"10.18632\/oncotarget.105","article-title":"Over-expression of CKS1B activates both MEK\/ERK and JAK\/STAT3 signaling pathways and promotes myeloma cell drug-resistance","volume":"1","author":"Shi","year":"2010","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.3324\/haematol.2021.278888","article-title":"Chromosome 1q21 abnormalities refine outcome prediction in patients with multiple myeloma\u2014A meta-analysis of 2,596 trial patients","volume":"106","author":"Weinhold","year":"2021","journal-title":"Haematologica"},{"key":"ref_16","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."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41408-022-00611-x","article-title":"A simple additive staging system for newly diagnosed multiple myeloma","volume":"12","author":"Abdallah","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_18","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. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41571-018-0018-y","article-title":"The multiple myelomas\u2014Current concepts in cytogenetic classification and therapy","volume":"15","author":"Kumar","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_20","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., and Vardiman, J.W. (2017). WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, IARC."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.humpath.2018.09.008","article-title":"IgM plasma cell myeloma in the era of novel therapy: A clinicopathological study of 17 cases","volume":"84","author":"Angelova","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/leu.2009.174","article-title":"International Myeloma Working Group molecular classification of multiple myeloma: Spotlight review","volume":"23","author":"Fonseca","year":"2009","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/gim.2016.50","article-title":"Section E6.1-6.4 of the ACMG technical standards and guidelines: Chromosome studies of neoplastic blood and bone marrow-acquired chromosomal abnormalities","volume":"18","author":"Mikhail","year":"2016","journal-title":"Genet. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e365","DOI":"10.1038\/bcj.2015.92","article-title":"Interpretation of cytogenetic results in multiple myeloma for clinical practice","volume":"5","author":"Rajan","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1001\/jamaoncol.2019.4659","article-title":"Moving from Cancer Burden to Cancer Genomics for Smoldering Myeloma: A Review","volume":"6","author":"Maura","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1200\/JCO.21.01987","article-title":"In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present from Diagnosis in Tiny, Undetectable Subclonal Populations","volume":"41","author":"Lannes","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/gcc.1189","article-title":"Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B-cell lymphoma and multiple myeloma","volume":"32","author":"Leroux","year":"2001","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.clml.2015.05.005","article-title":"Jumping Translocations in Myeloid Malignancies Associated with Treatment Resistance and Poor Survival","volume":"15","author":"Sanford","year":"2015","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1182\/blood.V91.5.1732","article-title":"Jumping translocations of chromosome 1q in multiple myeloma: Evidence for a mechanism involving decondensation of pericentromeric heterochromatin","volume":"91","author":"Sawyer","year":"1998","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1182\/blood-2006-07-038430","article-title":"A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1","volume":"109","author":"Shaughnessy","year":"2007","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1080\/10428194.2021.1964021","article-title":"Whole genome sequencing demonstrates substantial pathophysiological differences of MYC rearrangements in patients with plasma cell myeloma and B-cell lymphoma","volume":"62","author":"Bendig","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1182\/blood.V98.10.3082","article-title":"Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors","volume":"98","author":"Gerson","year":"2001","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1038\/leu.2014.70","article-title":"Promiscuous MYC locus rearrangements hijack enhancers but mostly super-enhancers to dysregulate MYC expression in multiple myeloma","volume":"28","author":"Affer","year":"2014","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1158\/1078-0432.CCR-20-2283","article-title":"Implications of MYC Rearrangements in Newly Diagnosed Multiple Myeloma","volume":"26","author":"Abdallah","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/ejh.13905","article-title":"Amp(1q) and tetraploidy are commonly acquired chromosomal abnormalities in relapsed multiple myeloma","volume":"110","author":"Locher","year":"2023","journal-title":"Eur. J. Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E117","DOI":"10.1002\/ajh.25420","article-title":"Tetraploidy is associated with poor prognosis at diagnosis in multiple myeloma","volume":"94","author":"Sidana","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.leukres.2010.01.013","article-title":"Near-tetraploidy clone can evolve from a hyperdiploidy clone and cause resistance to lenalidomide and bortezomib in a multiple myeloma patient","volume":"34","author":"Yuan","year":"2010","journal-title":"Leuk. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.cancergen.2014.06.027","article-title":"Change in ploidy status from hyperdiploid to near-tetraploid in multiple myeloma associated with bortezomib\/lenalidomide resistance","volume":"207","author":"Pavlistova","year":"2014","journal-title":"Cancer Genet."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/23\/5690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:36:27Z","timestamp":1760132187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/23\/5690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,2]]},"references-count":38,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["cancers15235690"],"URL":"https:\/\/doi.org\/10.3390\/cancers15235690","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,2]]}}}