Our major aim is to understand the changes in nuclei of aneuploid CNS neoplasms. Isolation and characterization of subsets of repeated sequences in mouse and human DNA will be continued, with emphasis on chromosomal structure (studied by in situ hybridization) and DNA analysis. Ultra-structural studies of the nucleolus organizing regions in interphase nuclei will be correlated with quantitative analysis of DNA restriction profiles from normal and neuroectodermal tumor cells using defined ribosomal DNA probes. Methods to analyze ribosomal and other DNA sequence subsets of interest, with respect to their sequence, distribution, and three-dimensional arrangement in chromosomes and interphase nuclei, are being pursued. Recent progress with biotin-labeled DNA probes has allowed high-resolution (EM) studies of specific DNA sequences in preparations of interphase and metaphase chromosomes. These studies indicate specific three-dimensional arrangements of selected DNA sequences in differentiated CNS cell types and significant alterations in CNS tumor cells. (I)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA015044-15
Application #
3164068
Study Section
Pathology A Study Section (PTHA)
Project Start
1977-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
15
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Manuelidis, L (1994) Genomic stability and instability in different neuroepithelial tumors. A role for chromosome structure? J Neurooncol 18:225-39
Taruscio, D; Manuelidis, L (1991) Integration site preferences of endogenous retroviruses. Chromosoma 101:141-56
Manuelidis, L (1991) Heterochromatic features of an 11-megabase transgene in brain cells. Proc Natl Acad Sci U S A 88:1049-53
Lamperth, L; Manuelidis, L; Webster, H D (1990) P0 glycoprotein mRNA distribution in myelin-forming Schwann cells of the developing rat trigeminal ganglion. J Neurocytol 19:756-64
Manuelidis, L (1990) A view of interphase chromosomes. Science 250:1533-40
Akowitz, A; Manuelidis, L (1989) A novel cDNA/PCR strategy for efficient cloning of small amounts of undefined RNA. Gene 81:295-306
Cremer, T; Tesin, D; Hopman, A H et al. (1988) Rapid interphase and metaphase assessment of specific chromosomal changes in neuroectodermal tumor cells by in situ hybridization with chemically modified DNA probes. Exp Cell Res 176:199-220
Borden, J; Manuelidis, L (1988) Movement of the X chromosome in epilepsy. Science 242:1687-91
Lichter, P; Cremer, T; Tang, C J et al. (1988) Rapid detection of human chromosome 21 aberrations by in situ hybridization. Proc Natl Acad Sci U S A 85:9664-8
Cremer, T; Lichter, P; Borden, J et al. (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes. Hum Genet 80:235-46

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