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

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