Medical Oncology Department, Puerta de Hierro University Hospital, Madrid, Spain.
Gastroenterology and Hepatology Department, Endoscopy Unit Puerta de Hierro University Hospital, Madrid, Spain.
Mol Genet Genomic Med. 2024 Jul;12(7):e2496. doi: 10.1002/mgg3.2496.
Hereditary diffuse gastric cancer (HDGC) (OMIM# 137215) is an autosomal dominant cancer syndrome associated with CDH1 (OMIM# 192090) mutations. Prophylactic total gastrectomy (PTG) is the most recommended preventive treatment when a pathogenic mutation is found. However, the increasing use of genetic testing has led to the identification of incidental CDH1 mutations in individuals without a family history of gastric cancer. It remains unclear whether these patients should undergo prophylactic total gastrectomy.
Germline DNA, obtained from peripheral blood, was analysed by NGS.
A 47-year-old woman was diagnosed with high-grade serous ovarian carcinoma, FIGO stage IIIC, with a Homologous Recombination Deficiency (HRD) GIS status of 78 (positive, cut-off: 43). She received chemotherapy and niraparib treatment. A multigene panel test revealed no pathogenic mutations in BRCA1 (OMIM# 113705)/BRCA2 (OMIM# 600185) genes, but a de novo deletion of exon 16 in CDH1 was found incidentally. She had no previous family history of gastric or breast cancer. The patient was enrolled in a surveillance program involving periodic endoscopy and was diagnosed with diffuse gastric cancer through biopsies of a pale area in the antrum after 1 year of close endoscopic follow-up.
This case presents supportive evidence for the pathogenic classification of the loss of the last exon of CDH1.
遗传性弥漫性胃癌（HDGC）（OMIM#137215）是一种常染色体显性遗传的癌症综合征，与 CDH1（OMIM#192090）基因突变有关。当发现致病突变时，预防性全胃切除术（PTG）是最推荐的预防治疗方法。然而，随着基因检测的广泛应用，在没有胃癌家族史的个体中发现了偶然的 CDH1 突变。目前尚不清楚这些患者是否应该进行预防性全胃切除术。
通过 NGS 分析外周血获得的种系 DNA。
一名 47 岁女性被诊断为高级别浆液性卵巢癌，FIGO 分期为 IIIIC，同源重组缺陷（HRD）GIS 状态为 78（阳性，临界值：43）。她接受了化疗和尼拉帕尼治疗。多基因panel 检测未发现 BRCA1（OMIM#113705）/BRCA2（OMIM#600185）基因突变，但偶然发现 CDH1 外显子 16 缺失。她以前没有胃癌或乳腺癌家族史。该患者参加了一个监测计划，包括定期内窥镜检查，在密切的内窥镜随访 1 年后，通过活检发现了胃窦部苍白区域，诊断为弥漫性胃癌。
本病例为 CDH1 最后一个外显子缺失的致病性分类提供了支持证据。
