Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population
Background and aims: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targe...
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MDPI AG
2020-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/2/510 |
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| author | Koki Nakamura Yuji Urabe Kenichi Kagemoto Ryo Yuge Ryohei Hayashi Atsushi Ono C. Nelson Hayes Shiro Oka Masanori Ito Takashi Nishisaka Kazuaki Tanabe Koji Arihiro Hideki Ohdan Shinji Tanaka Kazuaki Chayama |
| author_facet | Koki Nakamura Yuji Urabe Kenichi Kagemoto Ryo Yuge Ryohei Hayashi Atsushi Ono C. Nelson Hayes Shiro Oka Masanori Ito Takashi Nishisaka Kazuaki Tanabe Koji Arihiro Hideki Ohdan Shinji Tanaka Kazuaki Chayama |
| author_sort | Koki Nakamura |
| collection | DOAJ |
| description | Background and aims: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. Methods and results: We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. Conclusion: These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer. |
| first_indexed | 2024-03-12T20:13:11Z |
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| language | English |
| last_indexed | 2024-03-12T20:13:11Z |
| publishDate | 2020-02-01 |
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| series | Cancers |
| spelling | doaj.art-ffa5a3104b624a398cbf031852c17e242023-08-02T01:34:23ZengMDPI AGCancers2072-66942020-02-0112251010.3390/cancers12020510cancers12020510Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese PopulationKoki Nakamura0Yuji Urabe1Kenichi Kagemoto2Ryo Yuge3Ryohei Hayashi4Atsushi Ono5C. Nelson Hayes6Shiro Oka7Masanori Ito8Takashi Nishisaka9Kazuaki Tanabe10Koji Arihiro11Hideki Ohdan12Shinji Tanaka13Kazuaki Chayama14Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanDepartment of Pathology and Laboratory Medicine, Hiroshima Prefectural Hospital, Hiroshima 734-8551, JapanDepartment of Health Care for Adults, Graduate School of Biochemical & Health Sciences, Hiroshima 734-8551, JapanDepartment of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Hiroshima 734-8551, JapanDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biochemical & Health Sciences, Hiroshima 734-8551, JapanDepartment of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, JapanBackground and aims: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. Methods and results: We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. Conclusion: These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer.https://www.mdpi.com/2072-6694/12/2/510gastric cancerdriver mutationlrp1caga<i>helicobacter pylori</i> |
| spellingShingle | Koki Nakamura Yuji Urabe Kenichi Kagemoto Ryo Yuge Ryohei Hayashi Atsushi Ono C. Nelson Hayes Shiro Oka Masanori Ito Takashi Nishisaka Kazuaki Tanabe Koji Arihiro Hideki Ohdan Shinji Tanaka Kazuaki Chayama Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population Cancers gastric cancer driver mutation lrp1 caga <i>helicobacter pylori</i> |
| title | Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population |
| title_full | Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population |
| title_fullStr | Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population |
| title_full_unstemmed | Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population |
| title_short | Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population |
| title_sort | genomic characterization of non invasive differentiated type gastric cancer in the japanese population |
| topic | gastric cancer driver mutation lrp1 caga <i>helicobacter pylori</i> |
| url | https://www.mdpi.com/2072-6694/12/2/510 |
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