{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:20:26Z","timestamp":1765794026059,"version":"3.48.0"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Xeroderma Pigmentosum group C (XP-C) is an autosomal recessive disorder caused by mutations in the XPC gene, leading to defective nucleotide excision repair. This defect leads to genomic instability and a profound cancer predisposition. To model this disease, we generated induced pluripotent stem cells (iPSCs) from an XP-C patient carrying a novel homozygous nonsense mutation in the XPC gene (c.1830C&gt;A). The resulting iPSCs demonstrated typical pluripotent characteristics, including expression of key markers and trilineage differentiation capability. However, genomic assessment revealed progressive karyotypic instability during extended culture. While initial whole-genome sequencing detected no major chromosomal abnormalities, subsequent G-banding analysis identified acquired trisomy 12 in two lines (CL12 and CL27) and a derivative X chromosome in a third line (CL30). These abnormalities were absent in early-passage analyses, indicating that they were acquired and selected for during extended culture. The acquisition of a derivative X chromosome in CL30, alongside recurrent trisomy 12, represents a unique cytogenetic signature likely attributable to the underlying XPC defect. We hypothesize that the loss of GG-NER creates a permissive genomic environment, accelerating the accumulation of DNA damage and chromosomal missegregation under replicative stress. This temporal divergence in genomic integrity highlights how culture pressures drive chromosomal evolution in XP-C iPSCs independently of initial reprogramming. Our findings emphasize that XP-C iPSCs require continuous genomic surveillance and provide a model for investigating how DNA repair deficiencies interact with in vitro culture stress.<\/jats:p>","DOI":"10.3390\/cells14241985","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:11:23Z","timestamp":1765793483000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Karyotypic Profiling of Induced Pluripotent Stem Cells Derived from a Xeroderma Pigmentosum Group C Patient"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-0634","authenticated-orcid":false,"given":"Almaqdad","family":"Alsalloum","sequence":"first","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Mingaleva","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Gornostal","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoia","family":"Antysheva","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9160-0794","authenticated-orcid":false,"given":"Peter","family":"Sparber","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-3438","authenticated-orcid":false,"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8286-7924","authenticated-orcid":false,"given":"Victoria","family":"Pozhitnova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Belysheva","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, 127224 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aygun","family":"Levashova","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Suvorova","sequence":"additional","affiliation":[{"name":"Limited Liability Company \u201cBiotechnology Campus\u201d, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Krupinova","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"},{"name":"Moscow Clinical Scientific Center N.A. A.S. Loginov, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6377-9056","authenticated-orcid":false,"given":"Viktor","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5405-6729","authenticated-orcid":false,"given":"Alexej","family":"Abyzov","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-1601","authenticated-orcid":false,"given":"Olga","family":"Mityaeva","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"},{"name":"Department of Fundamental Medicine, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Volchkov","sequence":"additional","affiliation":[{"name":"Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia"},{"name":"Moscow Clinical Scientific Center N.A. A.S. Loginov, 111123 Moscow, Russia"},{"name":"Department of Fundamental Medicine, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nasrallah, N.A., Wiese, B.M., and Sears, C.R. (2022). Xeroderma Pigmentosum Complementation Group C (XPC): Emerging Roles in Non-Dermatologic Malignancies. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.846965"},{"key":"ref_2","first-page":"2","article-title":"DNA Damage and Gene Therapy of Xeroderma Pigmentosum, a Human DNA Repair-Deficient Disease","volume":"776","author":"Dupuy","year":"2015","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fassihi, H., Mohammed, S., Nakazawa, Y., Fawcett, H., Turner, S., Palfrey, J., Garrood, I., Abiona, A., Morley, A.M.S., and Shimada, M. (2025). 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