{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:32:57Z","timestamp":1781073177017,"version":"3.54.1"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"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: Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by a high incidence of skin cancers. These patients are deficient in nucleotide excision repair caused by mutations in one of the 7 XP genes. Methods: We diagnosed 181 XP patients using UV-induced DNA repair measurements and\/or DNA sequencing from 1982 to 2022 in France. Results: As all XP patients, the French ones are very sensitive to UV exposure but since they are usually very well protected, they develop relatively few skin cancers. A majority of French XP patients originate from North Africa and bear a founder mutation on the XPC gene. The striking discovery is that these patients are at a very high risk to develop aggressive and lethal internal tumors such as hematological malignancies (more than a 100-fold risk compared to the general population for myelodysplasia\/leukemia) with a median age of death of 25 years, and brain, gynecological, and thyroid tumors with even lower median ages of death. The high mutation rates found in XP-C internal tumors allow us to think that these XP patients could be successfully treated by immunotherapies. A full analysis of the molecular origins of these DNA repair-deficient tumors is discussed. Several explanations for this high predisposition risk are proposed. Conclusions: As the age of the XP population is increasing due to better photo-protection, the risk of lethal internal tumors is a new Damocles sword that hangs over XP-C patients. This review of the French cohort is of particular importance for alerting physicians and families to the prevention and early detection of aggressive internal tumors in XP patients.<\/jats:p>","DOI":"10.3390\/cancers15102706","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T01:37:24Z","timestamp":1683769044000},"page":"2706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The French Cohort of DNA Repair-Deficient Xeroderma Pigmentosum Patients: Risk of Hematological Malignancies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-6016","authenticated-orcid":false,"given":"Alain","family":"Sarasin","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche UMR9019 Centre National de la Recherche Scientifique, 94805 Villejuif, France"},{"name":"Gustave Roussy Institute, 94805 Villejuif, France"},{"name":"Universit\u00e9 Paris-Saclay, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nrm2549","article-title":"Transcription-coupled DNA repair: Two decades of progress and surprises","volume":"9","author":"Hanawalt","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","first-page":"562","article-title":"Xeroderma Pigmentosum: When the Sun Is the Enemy","volume":"Volume 3","author":"Sarasin","year":"2019","journal-title":"Encyclopedia of Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1136\/jmg.2010.083022","article-title":"Cancer and neurologic degeneration in xeroderma pigmentosum: Long term follow-up characterises the role of DNA repair","volume":"48","author":"Bradford","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1111\/bjd.12183","article-title":"Unexpected extradermatological findings in 31 patients with xeroderma pigmentosum type C","volume":"168","author":"Oriot","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.dnarep.2011.03.005","article-title":"A new XPC gene splicing mutation has led to the highest worldwide prevalence of xeroderma pigmentosum in black Mahori patients","volume":"10","author":"Cartault","year":"2011","journal-title":"DNA Repair"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1750-1172-6-70","article-title":"Xeroderma pigmentosum","volume":"6","author":"Lehmann","year":"2011","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18767","DOI":"10.1074\/jbc.M211838200","article-title":"Role of DNA polymerase eta in the UV mutation spectrum in human cells","volume":"278","author":"Stary","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/humu.22462","article-title":"Correlation of phenotype\/genotype in a cohort of 23 xeroderma pigmentosum-variant patients reveals 12 new disease-causing POLH mutations","volume":"35","author":"Opletalova","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.dnarep.2008.01.014","article-title":"Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy","volume":"7","author":"Kleijer","year":"2008","journal-title":"DNA Repair"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"221","DOI":"10.7326\/0003-4819-80-2-221","article-title":"Xeroderma pigmentosum. An inherited disease with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair","volume":"80","author":"Robbins","year":"1974","journal-title":"Ann. Intern. Med."},{"key":"ref_11","first-page":"1135","article-title":"Genetics and skin cancer of xeroderma pigmentosum in Japan","volume":"78","author":"Takebe","year":"1987","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/bjd.14046","article-title":"Clinical, genealogical and molecular investigation of the xeroderma pigmentosum type C complementation group in Tunisia","volume":"174","author":"Jerbi","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_13","first-page":"102","article-title":"Cyclobutane pyrimidine dimers are the main mutagenic DNA photoproducts in DNA repair-deficient trichothiodystrophy cells","volume":"58","author":"Marionnet","year":"1998","journal-title":"Cancer Res."},{"key":"ref_14","first-page":"1786","article-title":"Repair of DNA in human cells after treatment with activated aflatoxin B1","volume":"37","author":"Sarasin","year":"1977","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1056\/NEJMra0804615","article-title":"DNA damage, aging, and cancer","volume":"361","author":"Hoeijmakers","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1365-2133.1992.tb14845.x","article-title":"Prenatal diagnosis in a subset of trichothiodystrophy patients defective in DNA repair","volume":"127","author":"Sarasin","year":"1992","journal-title":"Br. J. Dermatol."},{"key":"ref_17","first-page":"185","article-title":"An immortalized xeroderma pigmentosum, group C, cell line which replicates SV40 shuttle vectors","volume":"183","author":"James","year":"1987","journal-title":"Mutat. Res."},{"key":"ref_18","first-page":"4402","article-title":"p53 mutations in skin and internal tumors of xeroderma pigmentosum patients belonging to the complementation group C","volume":"58","author":"Giglia","year":"1998","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/(SICI)1097-0215(19990505)81:3<345::AID-IJC6>3.0.CO;2-E","article-title":"Molecular analysis of glioma and skin-tumour alterations in a xeroderma-pigmentosum child","volume":"81","author":"Giglia","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1182\/blood-2019-01-895698","article-title":"Familial predisposition to TP53\/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum","volume":"133","author":"Sarasin","year":"2019","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5834","DOI":"10.1038\/s41467-020-19633-9","article-title":"XPC deficiency increases risk of hematologic malignancies through mutator phenotype and characteristic mutational signature","volume":"11","author":"Yurchenko","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13023-022-02203-1","article-title":"Increased risk of internal tumors in DNA repair-deficient xeroderma pigmentosum patients: Analysis of four international cohorts","volume":"17","author":"Nikolaev","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ejca.2021.03.022","article-title":"Combination of targeted therapy and immune checkpoint blocker in a patient with xeroderma pigmentosum presenting an aggressive angiosarcoma and a recurrent non-resectable basal cell carcinoma","volume":"150","author":"Boutros","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_24","unstructured":"Yurchenko, A.A., Fresneau, B., Borghese, B., Rajabi, F., Tata, Z., Genestie, C., Sarasin, A., and Nikolaev, S.I. Early-onset gynecological tumors in xeroderma pigmentosum group C patients, Commun. Med., in press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1385\/1-59259-973-7:009","article-title":"Complementation assays adapted for DNA repair-deficient keratinocytes","volume":"314","author":"Bergoglio","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/sj.gt.3300495","article-title":"Retrovirus mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C","volume":"4","author":"Zeng","year":"1997","journal-title":"Gene Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1038\/jid.2009.409","article-title":"A prevalent mutation with founder effect in xeroderma pigmentosum group C from North Africa","volume":"130","author":"Soufir","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","unstructured":"(2019). Hematological Malignancies, Sant\u00e9 Publique France. Available online: https:\/\/www.e-cancer.fr\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/bjhp.12375","article-title":"Psychological correlates of adherence to photoprotection in a rare disease: International survey of people with Xeroderma Pigmentosum","volume":"24","author":"Walburn","year":"2019","journal-title":"Br. J. Health Psychol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.dnarep.2009.10.003","article-title":"Effect of the anti-neoplastic drug doxorubicin on XPD-mutated DNA repair-deficient human cells","volume":"9","author":"Saffi","year":"2010","journal-title":"DNA Repair"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2169\/internalmedicine.56.7866","article-title":"Alert regarding Cisplatin-induced severe adverse events in cancer patients with xeroderma pigmentosum","volume":"56","author":"Sumiyoshi","year":"2017","journal-title":"Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1177\/10781552211038246","article-title":"Severe cisplatin-induced renal toxicity in a patient with xeroderma pigmentosum","volume":"28","author":"Gilbar","year":"2022","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_33","first-page":"5874","article-title":"Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide excision repair gene xeroderma pigmentosun group A antisense RNA in human lung adenocarcinoma cells","volume":"9","author":"Wu","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000342897","article-title":"Acute Megakaryoblastic Leukemia in a Patient with Xeroderma Pigmentosum: Discussion of Pathophysiological, Prognostic, and Toxicological Aspects","volume":"129","author":"Janjetovic","year":"2013","journal-title":"Acta Haematol."},{"key":"ref_35","unstructured":"Yurchenko, A., Rajabi, F., Braz-Petta, T., Fassihi, H., Lehmann, A.R., Nishigori, C., Wang, J., Padioleau, I., Gunbin, K., and Panunzi, L. Genomic mutation landscape of skin cancers from DNA repair-deficient xeroderma pigmentosum patients, Nat. Commun., in press."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Corradi, C., Vilar, J.B., Buzzatto, V.C., De Souza, T.A., Castro, L.P., Munford, V., De Vecchi, R., Galante, P., Orpinelli, F., and Miller, T. Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors. Carcinogenesis, 2023. in press.","DOI":"10.1101\/2022.07.28.22277756"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1038\/sj.emboj.7601277","article-title":"New functions of XPC in the protection of human skin cells from oxidative damage","volume":"25","author":"Parlanti","year":"2006","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.mad.2008.01.005","article-title":"Clinical implications of the basic defects in Cockayne syndrome and xeroderma pigmentosum and the DNA lesions responsible for cancer, neurodegeneration and aging","volume":"129","author":"Cleaver","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/gm343","article-title":"UVSSA and USP7: New players regulating transcription-coupled nucleotide excision repair in human cells","volume":"4","author":"Sarasin","year":"2012","journal-title":"Genome Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/humu.10179","article-title":"TP53 mutations in human skin cancers","volume":"21","author":"Sarasin","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/(SICI)1098-2744(199712)20:4<340::AID-MC3>3.0.CO;2-N","article-title":"prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes","volume":"20","author":"Dumaz","year":"1997","journal-title":"Mol. Carcinog."},{"key":"ref_42","first-page":"823","article-title":"Blockage of RNA polymerase as a possible trigger for u.v. light-induced apoptosis","volume":"13","author":"Ljungman","year":"1996","journal-title":"Oncogene"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrfmmm.2007.11.010","article-title":"Resistance to ultraviolet-induced apoptosis in DNA repair deficient growth arrested human fibroblasts is not related to recovery from RNA transcription blockage","volume":"640","author":"Quayle","year":"2008","journal-title":"Mutat. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.1038\/sj.onc.1203844","article-title":"Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair","volume":"19","author":"Wijnhoven","year":"2000","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gde.2013.11.014","article-title":"Mutational Signatures: The patterns of somatic mutations hidden in cancer genomes","volume":"24","author":"Alexandrov","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1073\/pnas.070471597","article-title":"Removal of oxygen free-radical-induced 5\u2032,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells","volume":"97","author":"Kuraoka","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.biochi.2003.11.005","article-title":"Transcription-coupled repair of 8-oxoguanine in human cells and its deficiency in some DNA repair diseases","volume":"85","author":"Sarasin","year":"2003","journal-title":"Biochimie"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1001\/archderm.1987.01660260111026","article-title":"Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases","volume":"123","author":"Kraemer","year":"1987","journal-title":"Arch. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E1236","DOI":"10.1073\/pnas.1519444113","article-title":"Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect","volume":"113","author":"Fassihi","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1007\/s40618-020-01451-x","article-title":"Thyroid Nodules in Xeroderma Pigmentosum Patients: A Feature of Premature Aging","volume":"44","author":"Kouatcheu","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.3324\/haematol.2019.223370","article-title":"Predisposition to hematologic malignancies in patients with xeroderma pigmentosum","volume":"105","author":"Oetjen","year":"2020","journal-title":"Haematologica"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/jid.2008.239","article-title":"Identification of XP complementation groups by recombinant adenovirus carrying DNA repair genes","volume":"129","author":"Leite","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1093\/carcin\/bgi204","article-title":"Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients","volume":"27","author":"Khan","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/toxsci\/kfu233","article-title":"Molecular mechanisms of Acrolein Toxicity: Relevance to Human Disease","volume":"143","author":"Moghe","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.1038\/s41598-022-08961-z","article-title":"Paraquat toxicity in different cell types of Swiss albino mice","volume":"12","author":"Kuloglu","year":"2022","journal-title":"Sci. Rep."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:32:29Z","timestamp":1760124749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cancers15102706"],"URL":"https:\/\/doi.org\/10.3390\/cancers15102706","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]}}}