Abstract

Cancer is caused, at least in part, by the mutation of specific genes. Understanding these genes and their function is crucial to the future development of cancer therapies and improved diagnostics. The objective of this application is to identify novel genes that are commonly mutated in human cancer, with a special emphasis on tumor suppressor genes in breast cancer. The major discovery tool will be representational difference analysis (RDA), a method that the investigators use to derive probes for the altered genomic DNA of tumors. They have used this method to identify over eight loci that are homozygously deleted in human breast cancer; and the PTEN tumor suppressor gene was identified in one of these. Nine other loci are under study. The method also will be used to detect rearrangements and viruses in tumors. In addition, they have developed new tools for transcriptional mapping and the genomic analysis that will be brought to bear on these problems. This project will interface with other ongoing projects and collaborations of the investigators' laboratory that aim to: 1) utilize large scale genomic sequencing and analysis for gene discovery; 2) understand the function of the genes mutated in cancer; 3) establish the clinical relevance of the genetic alterations at the loci the investigators discover; and 4) discover de novo germ line mutations causing inborn disorders in children.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA078544-01
Application #
2679594
Study Section
Genome Study Section (GNM)
Program Officer
Shen, Grace L
Project Start
1998-07-15
Project End
2002-04-30
Budget Start
1998-07-15
Budget End
1999-04-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724

  Publications

Navin, Nicholas E; Hicks, James (2010) Tracing the tumor lineage. Mol Oncol 4:267-83
Lakshmi, B; Hall, Ira M; Egan, Christopher et al. (2006) Mouse genomic representational oligonucleotide microarray analysis: detection of copy number variations in normal and tumor specimens. Proc Natl Acad Sci U S A 103:11234-9
Hicks, James; Krasnitz, Alexander; Lakshmi, B et al. (2006) Novel patterns of genome rearrangement and their association with survival in breast cancer. Genome Res 16:1465-79
Navin, Nicholas; Grubor, Vladimir; Hicks, Jim et al. (2006) PROBER: oligonucleotide FISH probe design software. Bioinformatics 22:2437-8
Zender, Lars; Spector, Mona S; Xue, Wen et al. (2006) Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125:1253-67
Pelham, Robert J; Rodgers, Linda; Hall, Ira et al. (2006) Identification of alterations in DNA copy number in host stromal cells during tumor progression. Proc Natl Acad Sci U S A 103:19848-53
Jobanputra, Vaidehi; Sebat, Jonathan; Troge, Jennifer et al. (2005) Application of ROMA (representational oligonucleotide microarray analysis) to patients with cytogenetic rearrangements. Genet Med 7:111-8
Hicks, J; Muthuswamy, L; Krasnitz, A et al. (2005) High-resolution ROMA CGH and FISH analysis of aneuploid and diploid breast tumors. Cold Spring Harb Symp Quant Biol 70:51-63
Sebat, Jonathan; Lakshmi, B; Troge, Jennifer et al. (2004) Large-scale copy number polymorphism in the human genome. Science 305:525-8
Olshen, Adam B; Venkatraman, E S; Lucito, Robert et al. (2004) Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 5:557-72

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