Genomic subtypes of stomach cancer have distinct treatment responses

The first large-scale genomic analysis of gastric cancer confirms that the disease consists of two discrete tumor types that respond differently to chemotherapy.

“Our study is the first to show that a proposed molecular classification of gastric cancer can identify genomic subtypes that respond differently to therapies, which is crucial in efforts to customize treatments for patients,” noted Patrick Tan, MD, PhD, in a statement describing his team's findings, which were published in Gastroenterology (2011;141[2]:476.e11-485.e11).

Tan, the senior author of the study, is an associate professor in the Cancer and Stem Cell Biology program at the Duke-National University of Singapore Graduate Medical School in Singapore, group leader at the Genome Institute of Singapore, and a senior investigator at the Cancer Sciences Institute of Singapore. By analyzing gene expression profiles for 37 gastric cancer cell lines, Tan's group identified two major intrinsic genomic subtypes: G-INT and G-DIF, thus adding greater specificity to the microscopic classifications developed in the 1960s. Known as the Lauren classification, this system broadly typed gastric tumor cells as intestinal or diffuse based on how they clumped together.

The subtypes discovered by Tan and colleagues had distinct patterns of gene expression and were able to forecast survival. Tumor samples from 521 patients confirmed the results.

Compared with the G-DIF cell lines, the G-INT cell lines were significantly more sensitive to 5-fluorouracil and oxaliplatin, but more resistant to cisplatin. This information lays the groundwork for more effective treatment approaches.

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