Muranaka Futoshi, Kise Emiko, Tokumaru Shigeo, Kitazawa Masato, Miyagawa Yusuke, Suga Tomoaki, Uehara Takeshi, Iwaya Mai, Kobayashi Shota, Sato Midori, Gomi Daisuke, Yamada Hidetaka, Sugimura Haruhiko, Kosho Tomoki, Soejima Yuji, Koizumi Tomonobu
Department of Surgery, Division of Gastroenterological, Transplantation and Pediatric Surgery, Hepato-Biliary-Pancreatic, Shinshu University School of Medicine, Matsumoto, Japan.
Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.
Discov Oncol. 2023 Jan 31;14(1):14. doi: 10.1007/s12672-023-00623-4.
Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1-3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan.
In this study we report the clinical courses of three cases with HDGC from a single Japanese family.
The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy.
It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries.
E-钙黏蛋白基因CDH1的胚系致病变异会导致遗传性弥漫性胃癌（HDGC），这是一种常染色体显性癌症综合征，占所有胃癌的1%至3%。在日本，携带CDH1变异的HDGC极为罕见。
在本研究中，我们报告了来自一个日本家庭的3例HDGC患者的临床病程。
先证者表现为进展期转移性胃癌，且被发现存在先前报道的CDH1杂合移码变异（NM_004360.3:c.1009_1010del:p.Ser337Phefs*12）。5名有风险的亲属在经过仔细的遗传咨询后接受了症状前分子检测，其中3人被分子诊断为变异阳性。对这些亲属进行了食管胃十二指肠镜检查，发现有异常的小的苍白黏膜斑、小溃疡病变以及无异常发现。此外，随机活检和靶向活检与3例HDGC的病理诊断相符，所有患者均接受了全预防性胃切除术。
对于HDGC患者的评估和管理，积极采用多学科和以家庭为导向的方法至关重要。值得注意的是，对疑似个体和家庭成员进行基因筛查是提高低发和高发胃癌国家检测率以及识别临床相关突变的决定性因素。
