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Medical Oncology

, 37:10 | Cite as

Cancer gene profiling explores the possible precision medicine for diffuse-type gastric adenocarcinoma

  • Marin Ishikawa
  • Hideyuki Hayashi
  • Naoya Sakamoto
  • Shinya Tanaka
  • Hiroshi NishiharaEmail author
Original Paper

Abstract

Diffuse type gastric cancer (DGC), a pathological subtype, is one of the most common malignant solid tumors, and mortality of this tumor is not negligible, especially in early-onset cancer patients. In fact, affirmative personalized treatments based on gene profile have not been established yet. The aim of this study was to provide the possible genotype-matched treatment for DGC through comprehensive examination of genomic variants and analysis of clinicopathological characteristics. We retrospectively studied 23 formalin-fixed, paraffin-embedded samples of patients diagnosed as DGC between January 2003 and December 2015 at the Department of Cancer Pathology, Hokkaido University Graduate School of Medicine. The cases were divided into two groups: early-onset (< 50 years old) and elderly-onset (≥ 50 years old) DGC groups. We performed targeted genomic sequencing using a 163 cancer-related gene panel. The sequencing data were analyzed using an original bioinformatics pipeline called GenomeJack and were clinicopathologically evaluated. Intestinal metaplasia and atrophy were highly observed in the adjacent non-cancerous mucosa in the elderly-onset DGC group compared with those in the early-onset DGC group. The number of somatic variants was significantly higher in the elderly-onset DGC group than in the early-onset DGC group. Fifteen patients (65.2%) harbored at least one genomic alteration of the potential target for genotype-matched treatment. In addition, one patient with hypermutation phenotype was diagnosed as Lynch syndrome due to MLH1 mutation, suggesting the sensitivity for the treatment with immune checkpoint inhibitors. Not only does our study demonstrated the potential utility of the targeted genomic sequencing approach for making informed therapeutic decisions, but it also sheds light on DGC pathogenesis and progression.

Keywords

Gastric cancer Genomic alteration Cancer gene profiling test Next generation sequencing (NGS) Precision medicine Genotype-matched treatment 

Abbreviations

GC

Gastric cancer

NGS

Next generation sequencing

EBV

Epstein-barr virus

DGC

Diffuse type of gastric cancer

FFPE

Formalin-fixed, paraffin embedded

TNM

Tumor-node-metastasis

IHC

Immunohistochemical

PARP

Poly ADP-ribose polymerase

HDAC

Histone deacetylase

EZH2

Enhancer of zeste homolog 2

BTK

Bruton’s tyrosine kinase

HER2

Human epidermal growth factor receptor 2

CDK

Cyclin-dependent kinase

FGFR

Fibroblast growth factor receptor

mTOR

Mammalian target of rapamycin

ASPP

Apoptosis-stimulating protein of p53

SHP2

Src homology 2 domain containing protein tyrosine phosphatase 2

FAK

Focal adhesion kinase

LOH

Loss of heterozygosity

Notes

Funding

This research is (partially) supported by the Program for an Integrated Database of Clinical and Genomic Information from Japan Agency for Medical Research and development (JP19ck0106406), AMED and also by Japan Society for the Promotion of Science (Grant Nos. 1 7 K 1 0 8 5 5, 1 7 K T 0 0 4 6).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12032_2019_1327_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 22 kb)
12032_2019_1327_MOESM2_ESM.pptx (3.1 mb)
Supplementary material 2 (PPTX 3136 kb)
12032_2019_1327_MOESM3_ESM.xlsx (36 kb)
Supplementary material 3 (XLSX 35 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of EndoscopyHokkaido University HospitalSapporoJapan
  2. 2.Department of Cancer PathologyHokkaido University Graduate School of MedicineSapporoJapan
  3. 3.Genomics Unit, Keio Cancer CenterKeio University School of MedicineTokyoJapan
  4. 4.Department of Gastroenterology and HepatologyHokkaido University Graduate School of MedicineSapporoJapan

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