Abstract 2722: Next generation targeted sequencing reveals four unknown mutations in the Mexican population with Gorlin syndrome

Abstract

Abstract Aim: Nevoid Basal Cell Carcinoma Syndrome (NBCCS), an autosomal dominant disorder, is characterized by the presence of a variety of developmental anomalies, and predisposition to multiple basal cell carcinomas (BCCs), and other neoplasias. NBCCS mainly results from germinal mutations in the PTCH1 gene, that encodes a transmembrane glycoprotein, component of the hedgehog signalling pathway. The incidence of NBCCS in general population is estimated at 1 in 150000. Data related to NBCCS in Mexican patients is reduced to clinical case reports, without molecular testing. Therefore, we conducted next-generation sequencing (NGS) of PTCH1, in 9 Mexican patients with diagnosis of NBCCS. Material and methods: NGS of PTCH1 was performed, in the context of a hereditary cancer gene panel. The PTCH1 regions with insufficient coverage (<30× read depth), were complemented by Sanger sequencing, to ensure 100% coverage of the gene. In-silico analysis was perfomed for missenses mutations. The identified pathogenic mutations were verified by capillary sequencing. Results: Targeted analysis of PTCH1 gene, looking for deletions, insertions, splice-site alterations, nonsense and missense mutations, was done. Four PTCH1 mutations (4/9) were identified: a deletion (c.1044delG); one insertion (c.631dupA); a non-sense mutation (c.3406G>T), and a missense mutation (c.1488C>A). None of the mutations had been previously reported. Conclusions : NGS of PTCH1 gene in 9 Mexican patients with clinical criteria for NBCCS allowed the identification of four novel pathogenic mutations (44% frequency). This is the first molecular overview of PTCH1 in NBCCS patients of our population. The perspectives of the current study lie in the molecular testing of other genes involved in NBCCS (PTCH2, SUFU), and other mechanisms (whole gene deletion), as well as the review of possible phenotype-genotype correlations. Citation Format: Fragoso Veronica, Natalia Espinosa, Julieta Dominguez, Felipe Vaca-Paniagua, Luis A. Herrera, Rosa M. Alvarez. Next generation targeted sequencing reveals four unknown mutations in the Mexican population with Gorlin syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2722. doi:10.1158/1538-7445.AM2017-2722