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Breast Cancer in Three Dimensions: Revealing Telomere Dysfunction in Breast Cancer

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Final rept. 23 Aug 2004-22 Aug 2005

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Forty three paraffin fixed tissue samples from anonymous hereditary and non-hereditary breast cancer cases were selected for the study. Five mum histological sections were prepared on microscopic slides for processing and analyses. All of the 43 tissue samples 11 nonhereditary 17 with a BRCA1 mutation 15 with a BRCA2 mutation were hybridized and imaged for telomere and centromere. Data recording on telomere organization and distribution are in progress. This work is expected to be completed by the end of 2005. Since we are using centromere signal intensity as a standard for relative fluorescence, we expect to complete the similar 3D image data obtained from the centromere signals obtained from these patient samples around the same time. We have data on telomere sizes and their frequency distribution patterns in the tumor cells of hereditary and non-hereditary breast cancer patients. We are currently doing statistical tests on these data to verify the sensitivity and effectiveness of our 3D measurement system. Our early results from studies using 3D telomere imaging system and quantization on cell lines with a BRCA1 mutation HCC1937 and with a BRCA2 mutation Capan-1 shows presence of significantly larger telomere aggregates in comparison to the telomeres of wild type MCF-7 cells p .0001 for comparisons between BRCA1 or BRCA2 and MCF-7. One hundred nuclei from each of MCF7, HCC1937 and Capan-1 have been examined and according to our data there are statistically significant differences in telomere sizes and their distribution patterns between the BRCA mutated HCC1937, Capan1 and wild type MCF7 cells. Our planned work on c-Myc deregulation has not commenced but we expect to start this in the near future.

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  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology

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