{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:33:30Z","timestamp":1790696010041,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,21]],"date-time":"2018-10-21T00:00:00Z","timestamp":1540080000000},"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>Myelodysplastic syndrome (MDS) can easily transform into acute myeloid leukemia (AML), a process which is often associated with clonal evolution and development of complex karyotypes. Deletion of 5q (del(5q)) is the most frequent aberration in complex karyotypes. This prompted us to analyze clonal evolution in MDS patients with del(5q). There were 1684 patients with low and intermediate-risk MDS and del(5q) with or without one additional cytogenetic abnormality, who were investigated cytogenetically in our department, involving standard karyotyping, fluorescence in situ hybridization (FISH) and multicolor FISH. We identified 134 patients (8%) with aspects of clonal evolution. There are two main routes of cytogenetic clonal evolution: a stepwise accumulation of cytogenetic events over time and a catastrophic event, which we defined as the occurrence of two or more aberrations present at the same time, leading to a sudden development of highly complex clones. Of the 134 patients, 61% underwent a stepwise accumulation of events whereas 39% displayed a catastrophic event. Patients with isolated del(5q) showed significantly more often a stepwise accumulation of events rather than a catastrophic event. The most frequent aberrations in the group of stepwise accumulation were trisomy 8 and trisomy 21 which were significantly more frequent in this group compared to the catastrophic event group. In the group with catastrophic events, del(7q)\/-7 and del(17p)\/-17 were the most common aberrations. A loss of 17p, containing the tumor suppressor gene TP53, was found significantly more frequent in this group compared to the group of stepwise accumulation. This leads to the assumption that the loss of TP53 is the driving force in patients with del(5q) who undergo a sudden catastrophic event and evolve into complex karyotypes.<\/jats:p>","DOI":"10.3390\/ijms19103269","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T08:43:36Z","timestamp":1540284216000},"page":"3269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Routes of Clonal Evolution into Complex Karyotypes in Myelodysplastic Syndrome Patients with 5q Deletion"],"prefix":"10.3390","volume":"19","author":[{"given":"Simone","family":"Feurstein","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"},{"name":"Department of Medicine, Section of Hematology\/Oncology, The University of Chicago, 900 E 57th street, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Thomay","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guntram","family":"Buesche","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Kreipe","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Thol","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Ganser","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Schlegelberger","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"G\u00f6hring","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1182\/blood-2012-03-420489","article-title":"Revised international prognostic scoring system for myelodysplastic syndromes","volume":"120","author":"Greenberg","year":"2012","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1182\/blood-2007-03-082404","article-title":"New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: Evidence from a core dataset of 2124 patients","volume":"110","author":"Haase","year":"2007","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nature10738","article-title":"Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing","volume":"481","author":"Ding","year":"2012","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1200\/JCO.2011.35.6394","article-title":"New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge","volume":"30","author":"Schanz","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41408-018-0061-z","article-title":"Detailed analysis of clonal evolution and cytogenetic evolution patterns in patients with myelodysplastic syndromes (MDS) and related myeloid disorders","volume":"8","author":"Schanz","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.leukres.2017.02.008","article-title":"New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types","volume":"57","author":"Strupp","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.leukres.2018.07.019","article-title":"The IPSS-R has prognostic impact in untreated patients with MDS del(5q)","volume":"72","author":"Kaivers","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/leu.2011.193","article-title":"Telomere shortening, clonal evolution and disease progression in myelodysplastic syndrome patients with 5q deletion treated with lenalidomide","volume":"26","author":"Lange","year":"2012","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00277-009-0846-z","article-title":"Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression","volume":"89","author":"Giagounidis","year":"2010","journal-title":"Ann. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1200\/JCO.2010.31.8576","article-title":"TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression","volume":"29","author":"Saft","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cell.2012.06.023","article-title":"The origin and evolution of mutations in acute myeloid leukemia","volume":"150","author":"Welch","year":"2012","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1056\/NEJMoa0912228","article-title":"Persistent malignant stem cells in del(5q) myelodysplasia in remission","volume":"363","author":"Tehranchi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature10762","article-title":"Clonal evolution in cancer","volume":"481","author":"Greaves","year":"2012","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1056\/NEJMoa1106968","article-title":"Clonal architecture of secondary acute myeloid leukemia","volume":"366","author":"Walter","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-I","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Abaigar, M., Robledo, C., Benito, R., Ramos, F., Diez-Campelo, M., Hermosin, L., Sanchez-Del-Real, J., Alonso, J.M., Cuello, R., and Megido, M. (2016). Chromothripsis Is a Recurrent Genomic Abnormality in High-Risk Myelodysplastic Syndromes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164370"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3324\/haematol.13024","article-title":"Frequent genomic abnormalities in acute myeloid leukemia\/myelodysplastic syndrome with normal karyotype","volume":"94","author":"Akagi","year":"2009","journal-title":"Haematologica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2010.11.055","article-title":"Massive genomic rearrangement acquired in a single catastrophic event during cancer development","volume":"144","author":"Stephens","year":"2011","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1093\/bioinformatics\/bti146","article-title":"CyDAS: A cytogenetic data analysis system","volume":"21","author":"Hiller","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/bjh.14636","article-title":"The 2016 revised World Health Organization definition of \u201cmyelodysplastic syndrome with isolated del(5q)\u201d; prognostic implications of single versus double cytogenetic abnormalities","volume":"178","author":"Gurney","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cell.2011.12.013","article-title":"Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations","volume":"148","author":"Rausch","year":"2012","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/bjh.12203","article-title":"TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis","volume":"160","author":"Kulasekararaj","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Schlegelberger, B., Metzke, S., Harder, S., Z\u00fchlke-Jenisch, R., Zhang, Y., and Siebert, R. (1999). Classical and molecular Cytogenetics of tumor cells. Diagnostic Cytogenetics, Springer.","DOI":"10.1007\/978-3-642-59918-7_9"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00277-007-0337-z","article-title":"Chromosomal aberrations in congenital bone marrow failure disorders--an early indicator for leukemogenesis?","volume":"86","author":"Karow","year":"2007","journal-title":"Ann. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.leukres.2009.10.027","article-title":"Recurrent involvement of heterochromatic regions in multiple myeloma-a multicolor FISH study","volume":"34","author":"Lange","year":"2010","journal-title":"Leuk. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3269\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:16Z","timestamp":1760196316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,21]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijms19103269"],"URL":"https:\/\/doi.org\/10.3390\/ijms19103269","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,21]]}}}