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ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2026

Clinicopathological and genomic features of extrachromosomal DNA in gastric cancer.

Yukio Hokazono, Mihoko Saito-Adachi, Natsuko Hama, Yasushi Totoki, Hiromi Nakamura, Yasuhito Arai, Shinichi Yachida, Akihiko Fukagawa, Hirofumi Rokutan, Tetsuo Ushiku and 1 more

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Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Yukio HokazonoDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Mihoko Saito-AdachiDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Natsuko HamaDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Yasushi TotokiDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Hiromi NakamuraDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Yasuhito AraiDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Shinichi YachidaDepartment of Cancer Genome Informatics, Graduate School of Medicine, The University of Osaka, Osaka, Japan.
Akihiko FukagawaDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Hirofumi RokutanDepartment of Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Tetsuo UshikuDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tatsuhiro ShibataDivision of Cancer Genomics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan. tashibat@ncc.go.jp.

Funding

Japan Agency for Medical Research and Development (AMED) 24ck01016800h0002National Cancer Center Research and Development Fund 2020-A-7
6 · The paper itself

Abstract

backgroundExtrachromosomal DNA (ecDNA), a form of circular DNA located outside chromosomes, is a common driver of oncogene amplification. Recent pan-cancer studies have associated ecDNA with cancer progression and poor prognosis. Moreover, its relationship with specific genomic features is becoming increasingly evident. However, the clinicopathological characteristics and underlying genomic mechanisms of ecDNA in gastric cancer remain poorly understood.

methodsWe analyzed whole-genome sequencing data from 81 Japanese gastric cancer samples to identify ecDNA using AmpliconArchitect and AmpliconClassifier. Gene expression profiles were obtained through whole-transcriptome RNA sequencing (RNA-seq).

resultsWe found that the frequency of ecDNA occurrence was comparable across cancer stages and had a modest impact on prognosis, suggesting that ecDNA is present in early-stage disease and has a limited role in gastric cancer progression. Several immunomodulatory genes were amplified on ecDNA, and the presence of ecDNA harboring these genes was associated with the suppression of cytotoxic T cell responses, indicating a functional link between ecDNA and immune evasion. ecDNA-positive cases more frequently harbored TP53 mutations and were microsatellite stable compared to ecDNA-negative cases. Finally, ecDNA-positive tumors exhibited a high prevalence of single-base substitution signature 17, implicating that oxidative stress, potentially induced by gastric acid, plays a role in the generation of ecDNA in gastric cancer.

conclusionsThese findings provide insights into the clinicogenomic features of ecDNA in gastric cancer and highlight its potential impact on disease progression and immune modulation.

Indexed as

Biomarkers, TumorDNA, CircularStomach NeoplasmsAgedFemaleHumansMaleMiddle AgedMutationPrognosisWhole Genome SequencingBiomarkers, TumorDNA, CircularGastric cancerGene amplificationGenomic structural variationWhole-genome sequencing

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.