New approach to gastric cancer classification based on TP53 mutation

Date

08 Oct 2016

Session

Poster Display

Presenters

Rie Makuuchi

Citation

Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371

Authors

R. Makuuchi1, K. Hatakeyama2, M. Terashima1, M. Kusuhara2, M. Tokunaga1, Y. Tanizawa1, E. Bando1, T. Kawamura1, M. Hikage1, S. Kaji1, K. Ohshima2, K. Urakami2, K. Yamaguchi2

Author affiliations

  • 1 Gastric Surgery, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 2 Research Institute, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
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Resources

Background

Recently, novel classifications based on molecular profiling have been advocated for various solid tumors. In gastric cancer, the Cancer Genome Atlas and the Asian Cancer Research Group (ACRG) have proposed a new classifications using genomic alterations. We previously reported that the ACRG classification was also applicable to Japanese patients. However, there was no difference of survival depending on TP53 activation signature, though progress between tumors of microsatellite instability (MSI) and epithelial-mesenchymal transition (EMT) was obviously different. The aim of this study is to propose a new classification which clearly categorize gastric cancer using TP53 tumor specific single nucleotide mutation.

Methods

We have launched a comprehensive molecular profiling in project HOPE (High-tech Omics-based Patient Evaluation) that analyzes genomes and transcriptomes of tumors obtained from the cancer patients admitted to Shizuoka Cancer Center from January 2014. Surgically-resected fresh tumor samples were analyzed by whole-exome sequencing (Ion Proton) and gene expression profiling (DNA microarray). A total of 188 patients with gastric cancer were included in this study. The patients were first subgrouped into MSI and EMT based on the ACRG classification. The remaining patients were then subgrouped by TP53 mutation status which depress its function (TP53+ and TP53-). Clinicopathological features and survival outcomes were compared among the groups.

Results

The number of patients classified into the MSI, EMT, TP53 + , and TP53- group was 21, 22, 15 and 130, respectively. The median follow-up period was 349 days. The patients were significantly younger in EMT. The undifferentiated type was significantly dominant in MSI. There was no statistically significant difference in tumor depth, lymph node metastasis, or tumor stage among the groups. Two-year cause-specific survival (CSS) rates were 95.5% in MSI, 49.9% in EMT, 65.5% in TP53 + , and 78.5% in TP53- (p = 0.048). Although the follow-up period was insufficient, CSS was worse in TP53+ than in TP53-.

Conclusions

Using a modified version of the ARGC classification focusing on TP53 mutation, we found that selected TP53 mutations is a potential factor to define the genotype of gastric cancer as well as MSI and EMT.

Clinical trial identification

Legal entity responsible for the study

Shizuoka Cancer Center

Funding

Shizuoka Cancer Center

Disclosure

All authors have declared no conflicts of interest.

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