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Recognition of and recent issues in hereditary diffuse gastric cancer

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Abstract

In East Asian countries, gastric cancer incidence is high, but detection rates for germline CDH1 mutations that cause hereditary diffuse gastric cancers (HDGCs) are low. Consequently, screens and genetic testing for HDGC are often considered unimportant. Since the first germline truncating CDH1 mutations in Japanese patients were reported, some HDGC cases have been reported, and some of these involve large germline rearrangements and de novo mutation of CDH1. New methods for mutation detection—such as multiplex ligation-dependent probe amplification, array comparative genomic hybridization, and exome sequencing—have become available, as have new experimental models, including novel gene-knockout mice and gastric organoids. Because of these advances, searches for candidate genes (e.g., CTNNA1, MAP3K6) and our understanding of HDGC pathogenesis have improved in recent years; moreover, there have been substantial changes in the field since the current HDGC consensus guidelines were released. This review focuses on recent issues and advances in the study of HDGC. For example, lobular breast cancer cases and de novo occurrences of DGC are unlikely to meet the existing criteria for genetic testing, but current evidence indicates that some such cases may be good candidates for genetic testing. It is important to recognize that HDGC is a syndrome and that lobular breast cancer can be the first manifestation of this syndrome. CDH1 testing, including analyses of large genomic rearrangements, should be recommended even in countries where few HDGC cases have been reported.

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Acknowledgment

We thank Hiroyuki Hayashi (Department of Pathology, Yokohama Municipal Citizen’s Hospital) for his help in preparing the figures and his helpful comments on pathology.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Shinya Sugimoto & Takanori Kanai

  2. Department of Gastroenterology, Yokohama Municipal Citizen’s Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan

    Hirokazu Komatsu & Yuichi Morohoshi

Authors
  1. Shinya Sugimoto
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  2. Hirokazu Komatsu
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  3. Yuichi Morohoshi
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  4. Takanori Kanai
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Correspondence to Shinya Sugimoto.

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Sugimoto, S., Komatsu, H., Morohoshi, Y. et al. Recognition of and recent issues in hereditary diffuse gastric cancer. J Gastroenterol 50, 831–843 (2015). https://doi.org/10.1007/s00535-015-1093-9

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  • DOI: https://doi.org/10.1007/s00535-015-1093-9

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