{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:34:03Z","timestamp":1777919643108,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 (ATM) 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 ATM 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 ATM-deficient cancers.<\/jats:p>","DOI":"10.3390\/genes12020313","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T14:23:27Z","timestamp":1614003807000},"page":"313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Novel ATM Pathogenic Variant in an Italian Woman with Gallbladder Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-0153","authenticated-orcid":false,"given":"Elisa","family":"De Paolis","sequence":"first","affiliation":[{"name":"Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-0719","authenticated-orcid":false,"given":"Lisa","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Foca","sequence":"additional","affiliation":[{"name":"Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giampaolo","family":"Tortora","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Medical Oncology, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Minucci","sequence":"additional","affiliation":[{"name":"Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0523-5744","authenticated-orcid":false,"given":"Paola","family":"Concolino","sequence":"additional","affiliation":[{"name":"Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12211","DOI":"10.3748\/wjg.v21.i43.12211","article-title":"Gallbladder carcinoma: Prognostic factors and therapeutic options","volume":"21","author":"Goetze","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"967472","DOI":"10.1155\/2015\/967472","article-title":"Gallbladder Cancer in the 21st Century","volume":"2015","author":"Kanthan","year":"2015","journal-title":"J. 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