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Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

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Technical Report,30 Sep 2014,29 Sep 2015

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DUKE UNIVERSITY Durham United States

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The project is designed to test whether genetic andor tumor environmental heterogeneity is a driving force in progression of breast DCIS. Our project, a collaboration between Duke and ASU, has made substantial progress on all 4 aims of the original proposal and is on track to meet 24 month milestones. Primary achievements during the first year are 1 Case and control identification through extensive database and medical record searching at Duke, 2 Development of methods for isolating DNA from archival DCIS lesions, 3 Deep and comprehensive full exome sequencing from 20ng of DNA isolated from these archival specimens, 4 Comparison of analytic methods to characterize somatic mutations from this full exome sequencing, 5 Application of sequencing library DNA to Illumina SNP arrays for copy number assessment, 6 Development of dual immune-staining on DCIS lesions using 7 pairs of antibodies, 7 Sharing of images from these stains with collaborators for quantitative analysis, 8 Identification of a series of upstaged DCIS cases for the radiology aim, 9 Development of image analysis methods for digital mammograms, 10 Approval of TBCRC protocol for the validation aim to initiate collection of DCIS that either did or did not progress to invasive cancer, 11 Full integration of team members over the past year via frequent conferencing, face to face meetings, and constant communication. This multi-disciplinary progress puts our group into an ideal position to fully implement the aims of the project and reach our intermediary and ultimate goals.

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