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

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...

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Bibliographic Details
Published in:Cancers 2020-02, Vol.12 (2), p.510
Main Authors: Nakamura, Koki, Urabe, Yuji, Kagemoto, Kenichi, Yuge, Ryo, Hayashi, Ryohei, Ono, Atsushi, Hayes, C Nelson, Oka, Shiro, Ito, Masanori, Nishisaka, Takashi, Tanabe, Kazuaki, Arihiro, Koji, Ohdan, Hideki, Tanaka, Shinji, Chayama, Kazuaki
Format: Article
Language:English
Subjects:
Age
Autophagy
Biopsy
Carcinogenesis
Endoscopy
Gastric cancer
Gastric mucosa
Gene expression
Genomes
Genomics
Infections
Kinases
Mutation
Nucleotide sequence
p53 Protein
Paraffin
Patients
Phagocytosis
Ribonucleic acid
RNA
Tumors
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Summary: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. 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. These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12020510