El-Husny Antonette, Raiol-Moraes Milene, Amador Marcos, Ribeiro-Dos-Santos André M, Montagnini André, Barbosa Silvanira, Silva Artur, Assumpção Paulo, Ishak Geraldo, Santos Sidney, Pinto Pablo, Cruz Aline, Ribeiro-Dos-Santos Ândrea
Laboratório de Genética Humana e Médica (LGHM), Instituto de Ciências Biológicas, Universidade Federal do Pará (UFPA), Belém, PA, Brazil.
Rede de Pesquisa em Genômica Populacional Humana, Universidade Federal do Pará (UFPA), Belém, PA, Brazil.
Genet Mol Biol. 2016 May 13;39(2):189-98. doi: 10.1590/1678-4685-GMB-2014-0342.
Gastric cancer is considered to be the fifth highest incident tumor worldwide and the third leading cause of cancer deaths. Developing regions report a higher number of sporadic cases, but there are only a few local studies related to hereditary cases of gastric cancer in Brazil to confirm this fact. CDH1 germline mutations have been described both in familial and sporadic cases, but there is only one recent molecular description of individuals from Brazil. In this study we performed Next Generation Sequencing (NGS) to assess CDH1 germline mutations in individuals who match the clinical criteria for Hereditary Diffuse Gastric Cancer (HDGC), or who exhibit very early diagnosis of gastric cancer. Among five probands we detected CDH1 germline mutations in two cases (40%). The mutation c.1023T > G was found in a HDGC family and the mutation c.1849G > A, which is nearly exclusive to African populations, was found in an early-onset case of gastric adenocarcinoma. The mutations described highlight the existence of gastric cancer cases caused by CDH1 germline mutations in northern Brazil, although such information is frequently ignored due to the existence of a large number of environmental factors locally. Our report represent the first CDH1 mutations in HDGC described from Brazil by an NGS platform.
胃癌被认为是全球第五大高发肿瘤，也是癌症死亡的第三大主要原因。发展中地区报告的散发病例数量较多，但在巴西，仅有少数关于遗传性胃癌病例的本地研究来证实这一事实。CDH1种系突变在家族性和散发病例中均有报道，但最近仅有一项对巴西个体的分子描述。在本研究中，我们进行了下一代测序（NGS），以评估符合遗传性弥漫性胃癌（HDGC）临床标准或胃癌诊断非常早的个体中的CDH1种系突变。在5名先证者中，我们在2例（40%）中检测到CDH1种系突变。在一个HDGC家族中发现了c.1023T>G突变，在一例早发性胃腺癌病例中发现了几乎仅见于非洲人群的c.1849G>A突变。所描述的突变凸显了巴西北部存在由CDH1种系突变引起的胃癌病例，尽管由于当地存在大量环境因素，此类信息常常被忽视。我们的报告是通过NGS平台描述的巴西HDGC中首个CDH1突变。
