López María, Cervera-Acedo Cristina, Santibáñez Paula, Salazar Raquel, Sola Jesús-Javier, Domínguez-Garrido Elena
Molecular Diagnostics Laboratory, Fundación Rioja Salud, Logroño, La Rioja Spain.
Department of Medical Oncology, Hospital San Pedro, Logroño, La Rioja Spain.
Springerplus. 2016 Jul 26;5(1):1181. doi: 10.1186/s40064-016-2852-7. eCollection 2016.
Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15-50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDGC harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of gastric adenocarcinoma and some of her relatives were tested. Study of the entire CDH1 gene, including intron-exon boundaries, by PCR and sequencing and immunohistochemical determination of the expression of E-cadherin were performed. A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC, p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a premature stop codon giving rise to a truncated protein that leads to a pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the proband's tumor but normal in tumor cells of great-uncle. After these results, the sister underwent prophylactic total gastrectomy, and the nephew is under annual endoscopic surveillance. Personal or familial history of diffuse gastric cancer, above all at young age, should encourage CDH1 genetic testing. In this sense, the review of the criteria and the addition in the last guideline of the recommendation: "other families in which genetic testing may also be considered" broadens the number of individuals at risk detected. Since there are not reliable methods for early detection, DGC is usually diagnosed at an advanced stage and consequently associated with a poorer outcome. Thus, CDH1 mutations detection contributes to an improvement in diagnosis and therapeutic intervention.
遗传性弥漫性胃癌（HDGC）是弥漫型胃癌的一种遗传形式。在符合HDGC临床标准的约15%-50%的受累家族中已鉴定出种系CDH1突变。如果符合任何一项标准，该个体将被转介进行遗传咨询并提供CDH1检测。在本报告中，我们介绍了一个患有HDGC且携带新型CDH1突变的西班牙家族的病例。一名诊断为胃腺癌的47岁女性及其一些亲属接受了检测。通过聚合酶链反应（PCR）和测序对整个CDH1基因（包括内含子-外显子边界）进行研究，并通过免疫组织化学法测定E-钙黏蛋白的表达。在先证者、一名姐妹和一个侄子中发现了CDH1基因外显子9中的一种新型杂合缺失（c.1220_1220delC，p.P407Qfs10）。它产生一个过早的终止密码子，导致截短的蛋白质，从而产生一个致病变异。先证者肿瘤中E-钙黏蛋白的表达缺失或明显降低，但叔祖父的肿瘤细胞中表达正常。基于这些结果，该姐妹接受了预防性全胃切除术，侄子接受每年一次的内镜监测。弥漫性胃癌的个人或家族史，尤其是在年轻时，应促使进行CDH1基因检测。从这个意义上说，对标准的审查以及在最新指南中增加“也可考虑进行基因检测的其他家族”这一建议，扩大了检测到的高危个体数量。由于没有可靠的早期检测方法，弥漫性胃癌通常在晚期被诊断出来，因此预后较差。因此，CDH1突变检测有助于改善诊断和治疗干预。
