I Technology Development

Any effort to understand cancer genomes in a comprehensive, systematic manner must address the technological hurdles of characterizing such a heterogeneous disease. The technological challenges include the need to: improve molecular characterization methods, such as gene expression, with respect to quality, throughput, and cost; further decrease the costs of DNA sequencing while maintaining quality; improve the detection and throughput of technologies for detecting epigenomic changes, while also decreasing cost; and develop new and better methods of correlating disease state with genomic changes.

Some high-throughput, cost-effective technologies needed for the analysis of the cancer genome are already in hand. However, further improvements in these technologies, as well as the development of innovative technologies, will be needed if The Cancer Genome Atlas (TCGA) is scaled up after the pilot project. TCGA is supporting technology development efforts in these areas.

The institutions receiving technology development awards include:

• Baylor College of Medicine, Houston; Aleksandar Milosavljevic, Ph.D.; $413,000; Comprehensive High-Throughput Mapping of Cancer Genomes. This project will develop methods to utilize new highly parallel DNA sequencing platforms to investigate structural variations in the genomes of cancer cells.

• City of Hope/Beckman Research Institute, Duarte, Calif.; Gerd Pfeifer, Ph.D.; $465,000; DNA Methylation in Cancer Genomes. These researchers will work on approaches for analyzing the methylation of DNA at high resolution across the genome using 1,000 cancer cells. Methylation, which involves the addition of methyl groups to the backbone of the DNA molecule, can change the way in which genes interact with the transcriptional machinery that turns genes on or off.

• Columbia University, New York; Benjamin Tycko, M.D., Ph.D.; $443,000; Genomic and Epigenomic Profiling by MSNP. This team will focus on using high-density oligonucleotide arrays to characterize genomic aberrations and DNA methylation. Oligonucleotides are short sequences of single-stranded DNA or RNA that are often used as probes for detecting complementary DNA or RNA because they bind readily to their complements.

• Columbia University, New York; Timothy Bestor, Ph.D.; $362,000; High-Throughput Profiling of Genomic Methylation Patterns. These researchers will develop methods for high-throughput, high-resolution profiling of DNA methylation.

• Johns Hopkins University, Baltimore; Andrew Feinberg, M.D., M.P.H.; $464,000; Functional Allelotyping.This group will generate new approaches for investigating allele-specific gene expression patterns. Allele is a term used by researchers to refer to the variant forms of a gene.

•  Nimblegen Systems, Inc., Madison, Wisc.; Thomas Albert, Ph.D.; $415,000. Large-Scale Selection of Genomic Loci. This team will use high-density oligonucleotide arrays in an innovative fashion to select genomic regions for DNA sequence analysis.

• Stanford University, Stanford, Calif; Ronald Davis, Ph.D.; $429,000. Development of Selectors for Cancer Mutation Analysis. This project will develop methods for high-throughput isolation of genomic regions for DNA sequence analysis.

• University of California-Davis; Peggy Farnham, Ph.D.; $418,000. Scaling the ChIP-chip Assay to Improve Analysis of Clinical Biospecimens. These researchers will work on methods that can be used to conduct high-throughput investigations of cancer-associated changes in genomic regions that are important in gene regulation, using small fragments of cancer tissue.

The technology development efforts will influence other key components of the TCGA Pilot Project: three Genome Sequencing Centers, seven Cancer Genome Characterization Centers, a Data Coordinating Center and a Biospecimen Core Resource.

To read more about the July 2007 technology development awards, click here.