I Technology Development
Advancing Cancer Genome Characterization and Sequencing Technologies
Any effort to understand cancer genomes in a comprehensive, systematic manner must address the technological hurdles of characterizing such a heterogeneous disease, including the need to:
- Improve the quality, throughput, and cost of gene expression and other molecular characterization methods;
- 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 more effective methods of correlating disease state with genomic changes.
Though some high-throughput, cost-effective technologies for cancer genome analyses already exist, further improvements are needed and new innovative approaches are required to address issues of small tumor size, cellular heterogeneity, and normal cell contamination. The TCGA project team is enabling technology development efforts to address these issues.
In 2007, the National Institutes of Health announced the award of eight two-year grants totaling $3.4 million to support the development of innovative technologies for exploring the genomic underpinnings of cancer as part of TCGA.
The technology development areas and institutions receiving awards include:
- Comprehensive High-Throughput Mapping of Cancer Genomes.
Baylor College of Medicine, Houston; Aleksandar Milosavljevic, Ph.D.; $413,000. The Baylor
research team is developing methods to utilize new, highly parallel DNA sequencing platforms to
investigate structural variations in the genomes of cancer cells.
- DNA Methylation in Cancer Genomes.
City of Hope/Beckman Research Institute, Duarte, Calif.; Gerd Pfeifer, Ph.D.; $465,000.
As part of this effort, researchers are working 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.
- Genomic and Epigenomic Profiling by MSNP.
Columbia University, New York; Benjamin Tycko, M.D., Ph.D.; $443,000. This team is focusing 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.
- High-Throughput Profiling of Genomic Methylation Patterns.
Columbia University, New York; Timothy Bestor, Ph.D.; $362,000. The Columbia research team is
developing methods for high-throughput, high-resolution profiling of DNA methylation.
- Functional Allelotyping.
Johns Hopkins University (JHU), Baltimore; Andrew Feinberg, M.D., M.P.H.; $464,000. As part of this
effort, JHU is supporting TCGA by generating 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.
- Large-Scale Selection of Genomic Loci.
Nimblegen Systems, Inc., Madison, Wisc.; Thomas Albert, Ph.D.; $415,000. This team is using
high-density oligonucleotide arrays in an innovative fashion to select genomic regions for DNA
- Development of Selectors for Cancer Mutation Analysis.
Stanford University, Stanford, Calif; Ronald Davis, Ph.D.; $429,000. This project is supporting
the technology goals of TCGA by developing methods for high-throughput isolation of genomic regions for
DNA sequence analysis.
- Scaling the ChIP-chip Assay to Improve Analysis of Clinical Biospecimens.
University of California-Davis; Peggy Farnham, Ph.D.; $418,000. These researchers are working 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.
These technology development grants are also working to advance the techonologies used
by the other key components of the Pilot Project, including TCGA Genome Sequencing Centers,
Cancer Genome Characterization Centers, Data Coordinating Center, and the Biospecimen Core Resource.