David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Gene-expression profiling identified three major disease subtypes with different responses to therapy.

Since the Lauren system of classifying gastric cancer was developed in 1965, the disease has been defined according to histologic features as either intestinal or diffuse. Can genetic data about gastric tumors provide additional information to inform therapy? To find out, investigators in Singapore identified the genetic expression of 248 gastric-tumor cell lines using microarray data from consensus hierarchical clustering with iterative feature selection.

The gene-expression profiles suggested three subtypes of gastric tumors — proliferative, metabolic, and mesenchymal — each with distinct genomic and epigenomic properties. The subtypes were validated in profiles of 70 tumors from Australian patients. Drug sensitivities of each type were based on clinical survival data and high-throughput screening of cell lines. The proliferative tumors had high genetic instability, TP53 mutations, and DNA hypomethylation. Metabolic tumors were more sensitive to 5-fluorouracil. Mesenchymal tumors had cells with features of stem cells and were more sensitive to phosphatidylinositol-3-kinase–AKT–mTOR inhibitors in vitro.

CITATION(S):

Lei Z et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology 2013 Sep; 145:554.