Hereditary diffuse gastric cancer in a Japanese family with CDH1 mutation three case reports

Futoshi Muranaka; Emiko Kise; Shigeo Tokumaru; Masato Kitazawa; Yusuke Miyagawa; Tomoaki Suga; Takeshi Uehara; Mai Iwaya; Shota Kobayashi; Midori Sato; Daisuke Gomi; Hidetaka Yamada; Haruhiko Sugimura; Tomoki Kosho; Yuji Soejima; Tomonobu Koizumi

doi:10.1007/s12672-023-00623-4

Hereditary diffuse gastric cancer in a Japanese family with CDH1 mutation three case reports

Discov Oncol. 2023 Jan 31;14(1):14. doi: 10.1007/s12672-023-00623-4.

Authors

Futoshi Muranaka¹, Emiko Kise², Shigeo Tokumaru¹, Masato Kitazawa¹, Yusuke Miyagawa¹, Tomoaki Suga³, Takeshi Uehara⁴, Mai Iwaya⁴, Shota Kobayashi⁴, Midori Sato⁵, Daisuke Gomi⁶, Hidetaka Yamada⁷, Haruhiko Sugimura⁷, Tomoki Kosho^{2

8

9

10}, Yuji Soejima¹, Tomonobu Koizumi¹¹

Affiliations

¹ Department of Surgery, Division of Gastroenterological, Transplantation and Pediatric Surgery, Hepato-Biliary-Pancreatic, Shinshu University School of Medicine, Matsumoto, Japan.
² Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.
³ Endoscopic Examination Center, Shinshu University Hospital, Matsumoto, Japan.
⁴ Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
⁵ Department of Pathology, Kurashiki Central Hospital, Kurashiki City, Japan.
⁶ Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
⁷ The First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
⁸ Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
⁹ Research Center for Supports to Advanced Science, Shinshu University, Matsumoto, Japan.
¹⁰ Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, Japan.
¹¹ Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan. tomonobu@shinshu-u.ac.jp.

Abstract

Background: 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.

Method: In this study we report the clinical courses of three cases with HDGC from a single Japanese family.

Results: 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.

Conclusion: 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.

Keywords: CDH1 mutations; E-cadherin; Esophagogastroduodenoscopy; Hereditary Diffuse Gastric Cancer; Random and target biopsies; Signet ring cell carcinoma; Total prophylactic gastrectomy.