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Abstract

Grant Number:	1R43CA103406-01
PI Name:	GUNDERSON, KEVIN L.
PI Email:	kgunderson@illumina.com
PI Title:
Project Title:	Representational analysis of DNA copy number/methylation

Abstract: DESCRIPTION (provided by applicant): Changes in methylation state and DNA copy number within the genome play a key role in cancer development and progression. Localization and quantification of these changes is important to the discovery of new tumor suppressor genes and oncogenes, and offers great potential in classifying cancer for clinical disease management. As such, the overall objective of this project is to develop a high-throughput array-based commercial technology to globally scan the genome for changes in DNA copy number (goal to detect two-fold differences) and methylation state. This will be accomplished via a reduced complexity representation approach using comparative genomic hybridization (CGH) and restriction landmark genome scanning (RLGS) technology on a BeadArrayTM platform. There are several immediate benefits offered by this representation approach. First of all, amplification of the representations will enhance signal to noise on the array. Secondly, improvements in generating representations will provide a more reproducible and robust process, allowing accurate detection of DNA copy number and methylation changes especially from archival samples exhibiting DNA degradation. Finally by converting RLGS from a 2-D gel-based approach (approximately 1000-2000 loci) to a BeadArrayTM-based analysis (approximately 1000-50,000 loci), a much higher locus resolution and sample throughput will be realized. This should enable the large-scale analysis of hundreds to thousands of tumor samples and lead to improved understanding of tumorogenesis. Phase II will apply this technology to the analysis of tumor samples and cell lines.

Thesaurus Terms:
DNA methylation, DNA replication, functional /structural genomics, genome, high throughput technology, representational difference analysis, technology /technique development
experimental design, genetic model, model design /development, restriction endonuclease, subtraction hybridization
human genetic material tag, microarray technology, polymerase chain reaction

Institution:	ILLUMINA, INC.
	9885 TOWNE CENTRE DR
	SAN DIEGO, CA 921211975
Fiscal Year:	2003
Department:
Project Start:	30-SEP-2003
Project End:	31-MAR-2004
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZRG1

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