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Genetic analysis of a case of Helicobacter pylori-uninfected intramucosal gastric cancer in a family with hereditary diffuse gastric cancer

  • Taro Funakoshi
  • Shin’ichi MiyamotoEmail author
  • Nobuyuki Kakiuchi
  • Mitsuhiro Nikaido
  • Takeshi Setoyama
  • Akira Yokoyama
  • Takahiro Horimatsu
  • Atsushi Yamada
  • Masako Torishima
  • Shinji Kosugi
  • Hidetaka Yamada
  • Haruhiko Sugimura
  • Hironori Haga
  • Yoshiharu Sakai
  • Seishi Ogawa
  • Hiroshi Seno
  • Manabu Muto
  • Tsutomu Chiba
Case Report
  • 177 Downloads

Abstract

Germline mutations in CDH1, encoding E-cadherin, are known to be the causative mechanism of hereditary diffuse gastric cancer (HDGC). We encountered two cases of gastric cancer in a Japanese family with HDGC. A 28-year-old man (Case 1) died of advanced gastric cancer. His younger sister aged 27 (Case 2) was diagnosed with intramucosal signet ring cell carcinoma (SRCC). Both had identical germline CDH1 mutations, but Case 1 was positive for Helicobacter pylori infection, whereas Case 2 was negative. Case 2 underwent total gastrectomy. Whole-exome sequencing of an intramucosal SRCC in Case 2 revealed seven somatic mutations including one in CDH1. The six non-CDH1 mutations were classified as non-driver mutations. Decreased expression of E-cadherin in intramucosal SRCC was confirmed by immunohistochemistry. Our report demonstrated that CDH1 mutation was the only active driver mutation in Helicobacter pylori-uninfected intramucosal SRCC.

Keywords

Hereditary diffuse gastric cancer Helicobacter pylori-uninfected gastric cancer Signet ring cell carcinoma CDH1 E-cadherin 

Notes

Acknowledgements

This research was supported by AMED under Grant Number JP18ck0106268 by National Cancer Center Research and Development Fund 28-A-1.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

This study was approved by the ethics committee of Kyoto University.

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  • Taro Funakoshi
    • 1
  • Shin’ichi Miyamoto
    • 2
    Email author
  • Nobuyuki Kakiuchi
    • 2
  • Mitsuhiro Nikaido
    • 2
  • Takeshi Setoyama
    • 3
  • Akira Yokoyama
    • 1
  • Takahiro Horimatsu
    • 1
  • Atsushi Yamada
    • 1
  • Masako Torishima
    • 4
  • Shinji Kosugi
    • 4
  • Hidetaka Yamada
    • 5
  • Haruhiko Sugimura
    • 5
  • Hironori Haga
    • 6
  • Yoshiharu Sakai
    • 7
  • Seishi Ogawa
    • 8
  • Hiroshi Seno
    • 2
  • Manabu Muto
    • 1
  • Tsutomu Chiba
    • 9
  1. 1.Department of Therapeutic Oncology, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto UniversityKyotoJapan
  3. 3.Department of Gastroenterology and HepatologyOsaka Red Cross HospitalOsakaJapan
  4. 4.Department of Medical Ethics and Medical GeneticsKyoto University School of Public HealthKyotoJapan
  5. 5.Department of Tumor PathologyHamamatsu University School of MedicineHamamatsuJapan
  6. 6.Department of Diagnostic Pathology, Graduate School of MedicineKyoto UniversityKyotoJapan
  7. 7.Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
  8. 8.Department of Pathology and Tumor Biology, Graduate School of MedicineKyoto UniversityKyotoJapan
  9. 9.Kansai Electric Power HospitalOsakaJapan

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