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Cells 2019, 8(2), 144;

Nevoid Basal Cell Carcinoma Syndrome: PTCH1 Mutation Profile and Expression of Genes Involved in the Hedgehog Pathway in Argentinian Patients

Laboratorio de Nefrología Experimental y Bioquímica Molecular, Instituto de Investigaciones Médicas “Alfredo Lanari”, Facultad de Medicina, Universidad de Buenos Aires, 1427 Buenos Aires, Argentina
Departamento de Análisis Clínicos, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”, 1431 Buenos Aires, Argentina
Unidad de Cirugía de MOHS, Departamento de Cirugía de Cabeza y Cuello, Instituto de Oncología “Ángel H. Roffo”, Facultad de Medicina, Universidad de Buenos Aires, 1408 Buenos Aires, Argentina
Buenos Aires Skin, 1055 Buenos Aires, Argentina
Servicio de Dermatología, Hospital Interzonal General de Agudos “Eva Perón”, 1650 Gral. San Martin, Argentina
Servicio de Dermatología, Hospital Italiano de Buenos Aires, 1199 Buenos Aires, Argentina
Author to whom correspondence should be addressed.
Received: 29 December 2018 / Revised: 25 January 2019 / Accepted: 2 February 2019 / Published: 11 February 2019
(This article belongs to the Special Issue Targeting Hedgehog Signaling in Cancer)
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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 < 0.05). NSS with PTCH1 germline mutations had modified SMO, PTCH1, and GLI3 mRNA levels compared to samples without mutation (p < 0.01). Two PTCH1 mutations in BCC led to an increase in PTCH1, SMO, and GLI3, and a decrease in CCND1 mRNA levels (p < 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. View Full-Text
Keywords: Gorlin–Goltz syndrome; PTCH1 mutation; Hedgehog pathway; basal cell carcinoma Gorlin–Goltz syndrome; PTCH1 mutation; Hedgehog pathway; basal cell carcinoma

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Martinez, M.F.; Romano, M.V.; Martinez, A.P.; González, A.; Muchnik, C.; Stengel, F.M.; Mazzuoccolo, L.D.; Azurmendi, P.J. Nevoid Basal Cell Carcinoma Syndrome: PTCH1 Mutation Profile and Expression of Genes Involved in the Hedgehog Pathway in Argentinian Patients. Cells 2019, 8, 144.

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