The major aspect of breast cancer progression is the accumulation of multiple genetic changes that contribute to an increasingly malignant phenotype. Changes include increased proliferation rate, reduced apoptosis, reduced adhesion and increased angiogenesis. Genetic instability can evolve at many different levels, everywhere from point mutations, to changes in chromosome. The level at which this instability occurs is not well known. Clarification of these issues is needed to improve our understanding of the neoplastic process. The investigator proposes to develop methods for analyzing genetic instability using archived paraffin embedded material to study the genetic instability in human breast ductal cell carcinoma. Their approach is to quantify the copy number of hybridization signals revealed using FISH with repeat sequence probes and later on with locus specific probes. They will determine the heterogeneity of copy number, the disease stage at which copy number changes are first detected and related parameters. Measurements will be made in normal tissue, areas of hyperplasia, in ductal cell carcinoma, and in invasive cancer. Questions to be asked include: Are there groups of cells homogenous with respect to copy number, or are differences detectable between adjacent cells? If a particular cell group appears homogenous, do other groups at the same stage display the same or different copy numbers? How does the degree of instability differ between stages within the same tumor? These studies require FISH analysis on fixed sections which are greater than 20 microns in thickness to ensure that most cells are intact. The analysis of the FISH images requires procedures for three dimensional image analysis that are not now available. Thus, a central goal of this project is to develop three dimensional image cytometry to support the studies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA067412-05
Application #
6150201
Study Section
Special Emphasis Panel (ZRG7-SSS-3 (22))
Program Officer
Lively, Tracy (LUGO)
Project Start
1996-02-20
Project End
2000-07-30
Budget Start
2000-02-01
Budget End
2000-07-30
Support Year
5
Fiscal Year
2000
Total Cost
$102,384
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
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