Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

J Transl Med. 2011 Jul 25:9:119. doi: 10.1186/1479-5876-9-119.

Abstract

Background: Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.

Methods: Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.

Results: Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.

Conclusions: The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.

MeSH terms

  • Cell Cycle Proteins / genetics
  • DNA Copy Number Variations / genetics
  • DNA, Neoplasm / genetics
  • Epithelium / metabolism
  • Epithelium / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Molecular Targeted Therapy
  • Mutation / genetics*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phenotype
  • Precision Medicine*
  • RNA, Neoplasm / genetics
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Signal Transduction / genetics
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DNA, Neoplasm
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Wnt Proteins