A Novel <i>ATM</i> Pathogenic Variant in an Italian Woman with Gallbladder Cancer

• Main Authors: Elisa De Paolis, Andrea Urbani, Lisa Salvatore, Laura Foca, Giampaolo Tortora, Angelo Minucci, Paola Concolino
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Genes
• Subjects: next-generation sequencing; <i>ATM</i> gene; gallbladder cancer; germline mutations
• Online Access: https://www.mdpi.com/2073-4425/12/2/313

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving different causative factors such as environmental, microbial, metabolic, and molecular. Genetic alterations can be germline or somatic that involving proto-oncogenes, tumor suppressor genes, cell cycle genes, and growth factors. The ataxia telangiectasia mutated (<i>ATM</i>) gene, coding a serine/threonine kinase involved in the early stages of the homologous recombination (HR) mechanism, is one of the most altered genes in GBC. Here, we present the molecular characterization of a novel germline <i>ATM</i> large genomic rearrangement (LGR) identified by next-generation sequencing (NGS) analysis in an Italian woman diagnosed with metastatic GBC at the age of 55. The results underline the importance of expanding the NGS approach in gallbladder cancer in order to propose new molecular markers of predisposition and prognosis exploitable by novel targeted therapies that may improve the response of patients with <i>ATM</i>-deficient cancers.