{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:49:41Z","timestamp":1768524581261,"version":"3.49.0"},"posted":{"date-parts":[[2025,7,19]]},"group-title":"Genomics","reference-count":12,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>We discovered a uniquely high spontaneous somatic mutational load in peripheral blood mononuclear cells (PBMCs) of Xeroderma Pigmentosum group C (XP-C) patients, characterized by elevated single nucleotide variants associated with mutation signatures SBS8 and SBS32, as well as an enrichment of single-nucleotide cytosine deletions. This hypermutability was markedly lower in fibroblasts, suggesting a replication-dependent mechanism of mutagenesis due to deficient global genome nucleotide excision repair (GG-NER). Our findings reveal distinct molecular subtypes within XP defined by spontaneous mutational load in normal blood cells and demonstrate that the exceptionally high mutation burden in XP-C leukemia originates from mutations already present prior to malignant transformation.<\/jats:p>","DOI":"10.1101\/2025.07.16.665113","type":"posted-content","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T05:10:14Z","timestamp":1752988214000},"source":"Crossref","is-referenced-by-count":0,"title":["Uniquely high spontaneous mutational load in blood cells of XP-C patients"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4435-5602","authenticated-orcid":false,"given":"Gordon","family":"Fan-Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8111-8382","authenticated-orcid":false,"given":"Elizabeth L.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moonsook","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5499-2963","authenticated-orcid":false,"given":"Shixiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Boull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheilagh M.","family":"Maguiness","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Vijg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1074-1385","authenticated-orcid":false,"given":"Laura J.","family":"Niedernhofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5402-8891","authenticated-orcid":false,"given":"Alexander Y.","family":"Maslov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025072215400914000_2025.07.16.665113v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3822"},{"key":"2025072215400914000_2025.07.16.665113v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.426"},{"key":"2025072215400914000_2025.07.16.665113v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19633-9"},{"key":"2025072215400914000_2025.07.16.665113v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2015.03.014"},{"key":"2025072215400914000_2025.07.16.665113v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm3259"},{"key":"2025072215400914000_2025.07.16.665113v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01119-5"},{"key":"2025072215400914000_2025.07.16.665113v1.7","doi-asserted-by":"publisher","DOI":"10.4161\/trns.1.2.12665"},{"key":"2025072215400914000_2025.07.16.665113v1.8","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.083022"},{"key":"2025072215400914000_2025.07.16.665113v1.9","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2000.65.61"},{"key":"2025072215400914000_2025.07.16.665113v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601277"},{"key":"2025072215400914000_2025.07.16.665113v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01182-9"},{"key":"2025072215400914000_2025.07.16.665113v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0539-0"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.16.665113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:09:33Z","timestamp":1768468173000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.07.16.665113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,19]]},"references-count":12,"URL":"https:\/\/doi.org\/10.1101\/2025.07.16.665113","relation":{},"subject":[],"published":{"date-parts":[[2025,7,19]]},"subtype":"preprint"}}