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Article

Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

1
Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
2
Department of Regeneration and Medicine Medical center for Translation and Clinical Research, Hiroshima University Hospital, Hiroshima 734-8551, Japan
3
Department of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan
4
Department of Pathology and Laboratory Medicine, Hiroshima Prefectural Hospital, Hiroshima 734-8551, Japan
5
Department of Health Care for Adults, Graduate School of Biochemical & Health Sciences, Hiroshima 734-8551, Japan
6
Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Hiroshima 734-8551, Japan
7
Department of Gastroenterological and Transplant Surgery, Graduate School of Biochemical & Health Sciences, Hiroshima 734-8551, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(2), 510; https://doi.org/10.3390/cancers12020510
Received: 28 January 2020 / Revised: 17 February 2020 / Accepted: 19 February 2020 / Published: 22 February 2020
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. View Full-Text
Keywords: gastric cancer; driver mutation; LRP1; CagA; Helicobacter pylori gastric cancer; driver mutation; LRP1; CagA; Helicobacter pylori
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MDPI and ACS Style

Nakamura, K.; Urabe, Y.; Kagemoto, K.; Yuge, R.; Hayashi, R.; Ono, A.; Hayes, C.N.; Oka, S.; Ito, M.; Nishisaka, T.; Tanabe, K.; Arihiro, K.; Ohdan, H.; Tanaka, S.; Chayama, K. Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population. Cancers 2020, 12, 510. https://doi.org/10.3390/cancers12020510

AMA Style

Nakamura K, Urabe Y, Kagemoto K, Yuge R, Hayashi R, Ono A, Hayes CN, Oka S, Ito M, Nishisaka T, Tanabe K, Arihiro K, Ohdan H, Tanaka S, Chayama K. Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population. Cancers. 2020; 12(2):510. https://doi.org/10.3390/cancers12020510

Chicago/Turabian Style

Nakamura, Koki, 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, and Kazuaki Chayama. 2020. "Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population" Cancers 12, no. 2: 510. https://doi.org/10.3390/cancers12020510

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