Acquired chromosomal and epigenetic changes in healthy cells following chemotherapy for breast cancer
Dr. Colleen Jackson-Cook
Wednesday, August 3, 2016
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Chapters
Introduction
First to hypothesize a role for chromosomes in cancer
Cytogenetics Methods
Breast Cancer One of most common forms of cancer in women (Gain, Loss and LOH)
Breast cancer tumor
New Insights for Breast Cancer Tumors
Breast Cancer
Breast Cancer Survivors pt.1
Breast Cancer Survivors pt.2
Is there an association between genetic and epigenetic changes and the development and persistence of psychoneurological (PN) symptoms associated with breast cancer treatment?
Breast Cancer flow chart
Longitudinal Study
Study Design
Methods: Acquired Chromosomal Instability Cytokinesis block MN/Cytome Assay
Is there a difference in MN frequencies in women with BC compared to controls?
Does the frequency of CIN change following treatment and does it differ based on the type of chemotherapy received?
Association of MN and perceived stress in women treated for BC
Does the variation in risk for developing PN symptoms also reflect attributes of the tumor itself?
Comparison of patterns between patients with breast cancer; Useful for stratification/prognosis
Comparison of MN in blood (baseline) to CN abnormalities in Breast Tumor
Chromothripsis
Hypothesized role of MN in chromothripsis – Pellman, et al.
Semi-quantitative FISH method for scoring telomere attrition
Do telomeres shorten following chemotherapy?
Heat map representation of % changes in telomere intensity values from baseline to mid-chemo
Significant correlations between chromosome-specific telomere length and depression
Association between telomere length and chemotherapy regimen?
Methods: Acquired Methylation Genome-wide (450K Assay)
Chart
What genes show changes in methylation that are common among the chemo regimens
Localization of DMRs compared to overall array distribution
Predicted chromatin states of DMRs compared to distribution on array
Chromosomal distribution of DMRs
Within DMRs, are there differences in CpGs having altered patterns between chemo regimens?
Genes having DMRs that differ between chemotherapy regimens:
Significant methylation changes:
Conclusions
Acknowledgements
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