{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:21:09Z","timestamp":1790871669827,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,4,27]]},"abstract":"<jats:p>\n                    Recently,\n                    <jats:italic>hptc<\/jats:italic>\n                    , a human gene homologous to the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    segment polarity gene\n                    <jats:italic>patched<\/jats:italic>\n                    (\n                    <jats:italic>ptc<\/jats:italic>\n                    ), has been implicated in the nevoid basal-cell carcinoma (BCC) syndrome, and somatic mutations of\n                    <jats:italic>hptc<\/jats:italic>\n                    also have been found in sporadic BCCs, the most frequent cancers found in the white population. We have analyzed the\n                    <jats:italic>hptc<\/jats:italic>\n                    gene, postulated to be a tumor suppressor gene, in 22 BCCs from patients with the hyperphotosensitive genodermatosis xeroderma pigmentosum (XP). Patients with XP are deficient in the repair of UV-induced DNA lesions and are characterized by their predisposition to cancers in sun-exposed skin. Analysis using PCR\u2013single-strand conformation polymorphism of the\n                    <jats:italic>hptc<\/jats:italic>\n                    gene identified 19 alterations in 16 of 22 (73%) of the BCCs examined. Only two (11%) deletions of the\n                    <jats:italic>hptc<\/jats:italic>\n                    gene were found in XP BCCs compared with &gt;30% rearrangement observed in non-XP sporadic BCCs, and 17 of 19 (89%) were base substitutions. Among the 17 base substitutions, 11 (65%) were CC \u2192 TT tandem mutations, and 4 (23%) were C \u2192 T substitutions, all targeted at bipyrimidine sites. Hence, a significantly higher number (15 of 19; 79%) of UV-specific alterations are seen in XP tumors, in contrast to non-XP sporadic BCCs. Interestingly, we have found that in 7 of 14 (50%) XP BCCs analyzed, both\n                    <jats:italic>hptc<\/jats:italic>\n                    and the tumor suppressor gene\n                    <jats:italic>p53<\/jats:italic>\n                    are mutated. Not only have our data indicated the key role played by\n                    <jats:italic>hptc<\/jats:italic>\n                    in the development of BCCs, they also have substantiated the link between unrepaired UV-induced DNA lesions and skin carcinogenesis, as exemplified by the UV-specific alterations of different genes in the same tumors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.9.5117","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"5117-5122","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":93,"title":["High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum"],"prefix":"10.1073","volume":"96","author":[{"given":"Nathalie","family":"Bodak","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Queille","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Fran\u00e7oise","family":"Avril","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakar","family":"Bouadjar","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Drougard","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Sarasin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leela","family":"Daya-Grosjean","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Institut de Recherches Scientifiques sur le Cancer, Bo\u00eete Postale 8, 94801 Villejuif, France; Department of Dermatology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France; and Department of Dermato-Venerology, Centre Hospitalo-Universitaire de Bab El Oued, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,4,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(91)70001-I"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198703000-00002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1994.01690030069011"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81268-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5268.1668"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/384176a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/384129a0"},{"key":"e_1_3_3_8_2","first-page":"M42","volume":"1332","author":"Dean M","year":"1997","unstructured":"M Dean Biochim Biophys Acta 1332, M42\u2013M52 (1997).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-78"},{"key":"e_1_3_3_10_2","first-page":"155","volume":"26","author":"Stary A","year":"1996","unstructured":"A Stary, A Sarasin Cancer Surv 26, 155\u2013171 (1996).","journal-title":"Cancer Surv"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.9103"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(94)90037-X"},{"key":"e_1_3_3_13_2","first-page":"1625","volume":"53","author":"Daya-Grosjean L","year":"1993","unstructured":"L Daya-Grosjean, C Robert, C Drougard, H Suarez, A Sarasin Cancer Res 53, 1625\u20131629 (1993).","journal-title":"Cancer Res"},{"key":"e_1_3_3_14_2","first-page":"4402","volume":"58","author":"Giglia G","year":"1998","unstructured":"G Giglia, N Dumaz, C Drougard, M Avril, L Daya-Grosjean, A Sarasin Cancer Res 58, 4402\u20134409 (1998).","journal-title":"Cancer Res"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10529"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/372773a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/1011-1344(95)07130-T"},{"key":"e_1_3_3_18_2","first-page":"4599","volume":"56","author":"Chidambaram A","year":"1996","unstructured":"A Chidambaram, A Goldstein, M Gailani, B Gerrard, S Bale, J DiGiovanna, A Bale, M Dean Cancer Res 56, 4599\u20134601 (1996).","journal-title":"Cancer Res"},{"key":"e_1_3_3_19_2","first-page":"2581","volume":"57","author":"Wolter M","year":"1997","unstructured":"M Wolter, J Reifenberger, C Sommer, T Ruzicka, G Reifenberger Cancer Res 57, 2581\u20132585 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.8.496"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.3.301"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1997.tb00370.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199802)21:2<87::AID-MC2>3.0.CO;2-L"},{"key":"e_1_3_3_24_2","first-page":"21","volume":"60","author":"Wicking C","year":"1997","unstructured":"C Wicking, S Shanley, I Smyth, S Gillies, K Negus, S Graham, G Suthers, N Haites, M Edwards, B Wainwright, et al. 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