Sequencing the Gastric Cancer Tumor Genome

Innovations in scientific and technology have led to an explosion in the Life Sciences field. The human genome has been mapped, new drugs have been introduced, molecular targets for cancer treatment and genetic determinants for cancer risk are being rapidly identified.   The Gastric Cancer Fund is well situated to leverage scientific and technology expertise to help better understand the genomic make-up of the gastric cancer cell, with the goal of trying to prevent its occurrence and eliminate it when it does.

Nowhere are the advances in biomedical innovation in cancer research more evident than the advent of “next generation” DNA sequencing technology.  These new DNA sequencer systems are revolutionizing biomedical research in cancer by generating DNA sequences up to the Gigabase range (> 1,000,000,000 nucleotides).

To accomplish the general goals of the gastric cancer registry, the organization will sponsor an overarching project to create a DNA sequence based digital compendium of the gastric cancer genome.  Investigators at Stanford University will use three separate approaches that will be integrated together to provide a high resolution overview of the gastric cancer genome.  First, they will use DNA sequencing to identify large errors that involve entire regions of the cancer genome, typically in the structures called chromosomes, delineate these complex changes of chromosomes, also known as rearrangements and their locations with a DNA sequencing process called paired-end analysis.

Second, they will selectively analyze targeted regions of the gastric cancer genome for specific mutations.  These regions will be chosen based on the likelihood that they contain cancer genes, partly extrapolated based on known cancer genes and genes occurring in the genomic aberrations discovered in the first approach.  Using resources at the Stanford Genome Technology Center, they selectively target any region of the gastric cancer genome and decode its information contents.  When combined with sequencing normal tissue from the same individual, the entire range of genetic errors in the genes can be understood.

Third, they will characterize the RNA transcriptome of gastric tumors.  This represents a second intermediate level of digital DNA code in which a different set of errors and aberrancies can occur.  Special emphasis will be placed on genes that are identified from the first two approaches.  When taken in combination, these multiple approaches provide a high resolution deconvolution of the gastric cancer genome and map the vast majority of errors which occur in each tumor.

The collated data from all three approaches will be used for a sophisticated analysis to root out the key molecular errors which contribute to gastric cancer development, clinical progression of cancer including recurrence and identify genetic modifiers of current and future drug targets of gastric cancer.  As a general resource, this information is invaluable in assisting researchers improve the clinical care of gastric cancer patients.