{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:28:05Z","timestamp":1790270885105,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"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>Background: Microsatellite and chromosomal instability have been investigated in Hodgkin lymphoma (HL). Materials and Methods: We studied seven HL cell lines (five Nodular Sclerosis (NS) and two Mixed Cellularity (MC)) and patient peripheral blood lymphocytes (100 NS-HL and 23 MC-HL). Microsatellite instability (MSI) was assessed by PCR. Chromosomal instability and telomere dysfunction were investigated by FISH. DNA repair mechanisms were studied by transcriptomic and molecular approaches. Results: In the cell lines, we observed high MSI in L428 (4\/5), KMH2, and HDLM2 (3\/5), low MSI in L540, L591, and SUP-HD1, and none in L1236. NS-HL cell lines showed telomere shortening, associated with alterations of nuclear shape. Small cells were characterized by telomere loss and deletion, leading to chromosomal fusion, large nucleoplasmic bridges, and breakage\/fusion\/bridge (B\/F\/B) cycles, leading to chromosomal instability. The MC-HL cell lines showed substantial heterogeneity of telomere length. Intrachromosmal double strand breaks induced dicentric chromosome formation, high levels of micronucleus formation, and small nucleoplasmic bridges. B\/F\/B cycles induced complex chromosomal rearrangements. We observed a similar pattern in circulating lymphocytes of NS-HL and MC-HL patients. Transcriptome analysis confirmed the differences in the DNA repair pathways between the NS and MC cell lines. In addition, the NS-HL cell lines were radiosensitive and the MC-cell lines resistant to apoptosis after radiation exposure. Conclusions: In mononuclear NS-HL cells, loss of telomere integrity may present the first step in the ongoing process of chromosomal instability. Here, we identified, MSI as an additional mechanism for genomic instability in HL.<\/jats:p>","DOI":"10.3390\/cancers10070233","type":"journal-article","created":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T04:05:33Z","timestamp":1531713933000},"page":"233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Independent Mechanisms Lead to Genomic Instability in Hodgkin Lymphoma: Microsatellite or Chromosomal Instability"],"prefix":"10.3390","volume":"10","author":[{"given":"Corina","family":"Cuceu","sequence":"first","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1742-8631","authenticated-orcid":false,"given":"Bruno","family":"Colicchio","sequence":"additional","affiliation":[{"name":"IRIMAS, Institut de Recherche en Informatique, Math\u00e9matiques, Automatique et Signal, Universit\u00e9 de Haute-Alsace, 68093 Mulhouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-0770","authenticated-orcid":false,"given":"Eric","family":"Jeandidier","sequence":"additional","affiliation":[{"name":"Department of Genetic, Groupe Hospitalier de la R\u00e9gion de Mulhouse Sud-Alsace, 68093 Mulhouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Junker","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Aarhus, DK-8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Plassa","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry B, Saint Louis Hospital, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Shim","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Mika","sequence":"additional","affiliation":[{"name":"Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Techology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5472-2373","authenticated-orcid":false,"given":"Monika","family":"Frenzel","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"AL Jawhari","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hempel","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Kabacik","sequence":"additional","affiliation":[{"name":"Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Lenain","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Morat","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Girinsky","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gustave Roussy Cancer Campus, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Dieterlen","sequence":"additional","affiliation":[{"name":"IRIMAS, Institut de Recherche en Informatique, Math\u00e9matiques, Automatique et Signal, Universit\u00e9 de Haute-Alsace, 68093 Mulhouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8004-9864","authenticated-orcid":false,"given":"Joanna","family":"Polanska","sequence":"additional","affiliation":[{"name":"Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Techology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-5008","authenticated-orcid":false,"given":"Christophe","family":"Badie","sequence":"additional","affiliation":[{"name":"Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot OX11 ORQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Carde","sequence":"additional","affiliation":[{"name":"Department of Medicine, Gustave Roussy Cancer Campus, University Paris Saclay, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhia","family":"M\u2019Kacher","sequence":"additional","affiliation":[{"name":"Radiobiology and Oncology Laboratory, CEA, iRCM, 92265 Fontenay aux Roses CEDEX, France"},{"name":"Cell Environment DNA Damages R&amp;D Oncology Section, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,13]]},"reference":[{"key":"ref_1","unstructured":"Stein, H., Delsol, G., Pileri, S., Weiss, L., Poppema, S., and Jaffe, E. 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