Multiancestry genomic and transcriptomic analysis of gastric cancer

doi:10.1038/s41588-023-01333-x

. 2023 Apr;55(4):581-594.

doi: 10.1038/s41588-023-01333-x. Epub 2023 Mar 13.

Multiancestry genomic and transcriptomic analysis of gastric cancer

Yasushi Totoki¹, Mihoko Saito-Adachi¹, Yuichi Shiraishi², Daisuke Komura³, Hiromi Nakamura¹, Akihiro Suzuki^{4

5}, Kenji Tatsuno⁵, Hirofumi Rokutan⁶, Natsuko Hama¹, Shogo Yamamoto⁵, Hanako Ono⁷, Yasuhito Arai¹, Fumie Hosoda¹, Hiroto Katoh³, Kenichi Chiba², Naoko Iida², Genta Nagae⁵, Hiroki Ueda⁸, Chen Shihang⁵, Shigeki Sekine⁹, Hiroyuki Abe⁶, Sachiyo Nomura¹⁰, Tetsuya Matsuura⁴, Eiji Sakai⁴, Takashi Ohshima¹¹, Yasushi Rino¹², Khay Guan Yeoh¹³, Jimmy So¹⁴, Kaushal Sanghvi¹⁵, Richie Soong¹⁶, Akihiko Fukagawa¹, Shinichi Yachida^{17

18}, Mamoru Kato⁷, Yasuyuki Seto¹⁰, Tetsuo Ushiku⁶, Atsushi Nakajima⁴, Hitoshi Katai¹⁹, Patrick Tan^{20

21}, Shumpei Ishikawa³, Hiroyuki Aburatani⁵, Tatsuhiro Shibata^{22

23}

Affiliations

¹ Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
² Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo, Japan.
³ Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
⁵ Genome Science and Medicine Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
⁶ Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁷ Division of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan.
⁸ Biological Data Science, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
⁹ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
¹⁰ Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹¹ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan.
¹² Department of Surgery, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
¹³ Dept of Medicine, National University of Singapore, Singapore, Singapore.
¹⁴ Dept of Surgery, National University of Singapore, Singapore, Singapore.
¹⁵ Dept of Surgery, Tan Tock Seng Hospital, Singapore, Singapore.
¹⁶ Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
¹⁷ Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹⁸ Division of Genomic Medicine, National Cancer Center Research Institute, Tokyo, Japan.
¹⁹ Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
²⁰ Cancer and Stem Cell Biology, Duke-NUS Medical School Singapore, Singapore, Singapore.
²¹ Epigenomic and Epitranscriptomic Regulation, Genome Institute of Singapore, Singapore, Singapore.
²² Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan. tshibata@ims.u-tokyo.ac.jp.
²³ Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. tshibata@ims.u-tokyo.ac.jp.

PMID: 36914835
DOI: 10.1038/s41588-023-01333-x

Multiancestry genomic and transcriptomic analysis of gastric cancer

Yasushi Totoki et al. Nat Genet. 2023 Apr.

. 2023 Apr;55(4):581-594.

doi: 10.1038/s41588-023-01333-x. Epub 2023 Mar 13.

Authors

Affiliations

¹ Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
² Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo, Japan.
³ Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
⁵ Genome Science and Medicine Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
⁶ Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁷ Division of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan.
⁸ Biological Data Science, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
⁹ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
¹⁰ Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹¹ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan.
¹² Department of Surgery, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
¹³ Dept of Medicine, National University of Singapore, Singapore, Singapore.
¹⁴ Dept of Surgery, National University of Singapore, Singapore, Singapore.
¹⁵ Dept of Surgery, Tan Tock Seng Hospital, Singapore, Singapore.
¹⁶ Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
¹⁷ Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹⁸ Division of Genomic Medicine, National Cancer Center Research Institute, Tokyo, Japan.
¹⁹ Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
²⁰ Cancer and Stem Cell Biology, Duke-NUS Medical School Singapore, Singapore, Singapore.
²¹ Epigenomic and Epitranscriptomic Regulation, Genome Institute of Singapore, Singapore, Singapore.
²² Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan. tshibata@ims.u-tokyo.ac.jp.
²³ Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. tshibata@ims.u-tokyo.ac.jp.

PMID: 36914835
DOI: 10.1038/s41588-023-01333-x

Abstract

Gastric cancer is among the most common malignancies worldwide, characterized by geographical, epidemiological and histological heterogeneity. Here, we report an extensive, multiancestral landscape of driver events in gastric cancer, involving 1,335 cases. Seventy-seven significantly mutated genes (SMGs) were identified, including ARHGAP5 and TRIM49C. We also identified subtype-specific drivers, including PIGR and SOX9, which were enriched in the diffuse subtype of the disease. SMGs also varied according to Epstein-Barr virus infection status and ancestry. Non-protein-truncating CDH1 mutations, which are characterized by in-frame splicing alterations, targeted localized extracellular domains and uniquely occurred in sporadic diffuse-type cases. In patients with gastric cancer with East Asian ancestry, our data suggested a link between alcohol consumption or metabolism and the development of RHOA mutations. Moreover, mutations with potential roles in immune evasion were identified. Overall, these data provide comprehensive insights into the molecular landscape of gastric cancer across various subtypes and ancestries.

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References

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1. Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). - DOI - PubMed
1. Parsonnet, J. et al. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325, 1127–1131 (1991). - DOI - PubMed
1. Kumar, S., Metz, D. C., Ellenberg, S., Kaplan, D. E. & Goldberg, D. S. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology 158, 527–536 (2020).
1. Smyth, E. C., Nilsson, M., Grabsch, H. I., van Grieken, N. C. & Lordick, F. Gastric cancer. Lancet 396, 635–648 (2020). - DOI - PubMed

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[1] Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018). - DOI - PubMed

[2] Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018). - DOI - PubMed

[3] Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). - DOI - PubMed

[4] Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). - DOI - PubMed

[5] Parsonnet, J. et al. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325, 1127–1131 (1991). - DOI - PubMed

[6] Parsonnet, J. et al. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325, 1127–1131 (1991). - DOI - PubMed

[7] Kumar, S., Metz, D. C., Ellenberg, S., Kaplan, D. E. & Goldberg, D. S. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology 158, 527–536 (2020).

[8] Kumar, S., Metz, D. C., Ellenberg, S., Kaplan, D. E. & Goldberg, D. S. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology 158, 527–536 (2020).

[9] Smyth, E. C., Nilsson, M., Grabsch, H. I., van Grieken, N. C. & Lordick, F. Gastric cancer. Lancet 396, 635–648 (2020). - DOI - PubMed

[10] Smyth, E. C., Nilsson, M., Grabsch, H. I., van Grieken, N. C. & Lordick, F. Gastric cancer. Lancet 396, 635–648 (2020). - DOI - PubMed

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Multiancestry genomic and transcriptomic analysis of gastric cancer

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Multiancestry genomic and transcriptomic analysis of gastric cancer

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