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Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

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[Technical Report, Annual Report]

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The project is designed to test whether genetic andor tumor environmental heterogeneity is a driving force inprogression of breast DCIS. Our project, a collaboration between Duke and ASU, have met our 60 month milestones in all 4 aims.Primary achievements for 60 months are1 Completed Case and control identification of 57 Pure DCIS and 61 Synchronous DCIS DCIS with adjacent invasion throughextensive database and searching at Duke 2 Completed deep whole exome sequencing WES for 100 cases from 30-160ng of DNAisolated from archival FFPE specimens, 3 Comparison of analytic methods to characterize somatic mutations from this full exomesequencing, 4 Application of sequencing data for copy number assessment 5 Completed dual immune-staining on DCIS lesionsusing 6 pairs and 3 single antibodies, 6 Completed Image analysis of these stains, including quantitative analysis, 7 Completedidentification of upstaged DCIS cases for the radiology aim, 8 Development of image analysis methods for digital mammograms, 9Completed the validation Aim 4, including collection of DCIS that either did not progress or progressed to DCIS or invasive cancer,10 Completed Aim 4 WES and Whole genome sequencing for 110 validation cases from 30-160ng of DNA isolated from archivalFFPE 11 Full integration of team members over the past year via frequent conferencing, face to face meetings, and constantcommunication. This multi-disciplinary approach allowed our group to fully implement and we reach our year 5 project goals.

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[A, Approved For Public Release]