Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.
Genes (Basel). 2021 Feb 22;12(2):313. doi: 10.3390/genes12020313.
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 () 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 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 -deficient cancers.
胆囊癌 (GBC) 是一种侵袭性最强的恶性肿瘤之一，预后不良，死亡率高。该疾病在晚期出现，治疗效果不佳。关于 GBC 的发病机制，与其他肿瘤一样，这种肿瘤是一种涉及不同致病因素的多因素疾病，如环境、微生物、代谢和分子因素。遗传改变可以是种系或体细胞的，涉及原癌基因、肿瘤抑制基因、细胞周期基因和生长因子。共济失调毛细血管扩张突变 () 基因，编码一种丝氨酸/苏氨酸激酶，参与同源重组 (HR) 机制的早期阶段，是 GBC 中改变最明显的基因之一。在这里，我们通过下一代测序 (NGS) 分析，在一名 55 岁被诊断为转移性 GBC 的意大利女性中发现了一种新的种系 大片段基因组重排 (LGR)，对其进行了分子特征描述。这些结果强调了在胆囊癌中扩大 NGS 方法的重要性，以便提出新的易感性和预后的分子标志物，利用新的靶向治疗来改善 - 缺陷癌症患者的反应。
