{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:55:32Z","timestamp":1790643332366,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003033","name":"Ministerio de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n Productiva","doi-asserted-by":"publisher","award":["Pr\u00e9stamo BID-PICT 2013-2461"],"award-info":[{"award-number":["Pr\u00e9stamo BID-PICT 2013-2461"]}],"id":[{"id":"10.13039\/501100003033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n del Cancer de Piel Argentina","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCC), mainly caused by PTCH1 gene mutations. Our current study aimed to establish (1) PTCH1 germinal and somatic mutational status, (2) component and Hedgehog (HH) pathway targets gene expression patterns, and (3) profile variations according to the genetic background in BCC and normal surrounding skin (NSS). We collected 23 blood and 20 BCC patient samples and analyzed the PTCH1 gene using bidirectional sequencing and multiplex ligation-dependent probe amplification. Quantitative PCR was used to determine the mRNA expression levels of PTCH1, SMO, GLI3, and CCND1 in paired samples of BCC and NSS from 20 patients and four non-NBCCS skin controls (C). Our analyses identified 12 germline and five somatic sequence variants in PTCH1. mRNA levels of PTCH1, SMO, and GLI3 were higher in NSS compared to C samples, reaching maximum values in BCC samples (p &lt; 0.05). NSS with PTCH1 germline mutations had modified SMO, PTCH1, and GLI3 mRNA levels compared to samples without mutation (p &lt; 0.01). Two PTCH1 mutations in BCC led to an increase in PTCH1, SMO, and GLI3, and a decrease in CCND1 mRNA levels (p &lt; 0.01 vs. BCC with germline mutation only). These results indicate that besides PTCH1, other genes are responsible for NBCCS and BCC development in a population exposed to high UV radiation. Additionally, the mutational events caused increased expression of HH-related genes, even in phenotypically normal skin.<\/jats:p>","DOI":"10.3390\/cells8020144","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Nevoid Basal Cell Carcinoma Syndrome: PTCH1 Mutation Profile and Expression of Genes Involved in the Hedgehog Pathway in Argentinian Patients"],"prefix":"10.3390","volume":"8","author":[{"given":"Maria Florencia","family":"Martinez","sequence":"first","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental y Bioqu\u00edmica Molecular, Instituto de Investigaciones M\u00e9dicas \u201cAlfredo Lanari\u201d, Facultad de Medicina, Universidad de Buenos Aires, 1427 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vanesa","family":"Romano","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lisis Cl\u00ednicos, Centro de Educaci\u00f3n M\u00e9dica e Investigaciones Cl\u00ednicas \u201cNorberto Quirno\u201d, 1431 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo Pedro","family":"Martinez","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lisis Cl\u00ednicos, Centro de Educaci\u00f3n M\u00e9dica e Investigaciones Cl\u00ednicas \u201cNorberto Quirno\u201d, 1431 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Unidad de Cirug\u00eda de MOHS, Departamento de Cirug\u00eda de Cabeza y Cuello, Instituto de Oncolog\u00eda \u201c\u00c1ngel H. Roffo\u201d, Facultad de Medicina, Universidad de Buenos Aires, 1408 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-3706","authenticated-orcid":false,"given":"Carolina","family":"Muchnik","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental y Bioqu\u00edmica Molecular, Instituto de Investigaciones M\u00e9dicas \u201cAlfredo Lanari\u201d, Facultad de Medicina, Universidad de Buenos Aires, 1427 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Miguel","family":"Stengel","sequence":"additional","affiliation":[{"name":"Buenos Aires Skin, 1055 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6315-7916","authenticated-orcid":false,"given":"Luis Daniel","family":"Mazzuoccolo","sequence":"additional","affiliation":[{"name":"Servicio de Dermatolog\u00eda, Hospital Interzonal General de Agudos \u201cEva Per\u00f3n\u201d, 1650 Gral. San Martin, Argentina"},{"name":"Servicio de Dermatolog\u00eda, Hospital Italiano de Buenos Aires, 1199 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7787-5882","authenticated-orcid":false,"given":"Pablo Javier","family":"Azurmendi","sequence":"additional","affiliation":[{"name":"Laboratorio de Nefrolog\u00eda Experimental y Bioqu\u00edmica Molecular, Instituto de Investigaciones M\u00e9dicas \u201cAlfredo Lanari\u201d, Facultad de Medicina, Universidad de Buenos Aires, 1427 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/01.GIM.0000144188.15902.C4","article-title":"Nevoid basal cell carcinoma (Gorlin) syndrome","volume":"6","author":"Gorlin","year":"2004","journal-title":"Genet. 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