1. Maxwell Lee National Cancer Institute Center for Cancer Research High-dimension Data Analysis Group March 19, 2014 Integrated Studies Of Breast, Esophageal, And Gastric Cancers Using High Throughput Technologies And Computational Analyses

2. Collaborators

3. Breast cancer 1.Delineating genetic alterations for tumor progression in the MCF10A series of cell lines. 2.Identifying novel oncogenes and functional studies 3.Predicting clinical outcome using DNA methylation and gene expression signatures Esophageal and gastric cancers 1.Microarray data analyses 2.Whole genome sequencing data analyses Outline Of The Talk

4. 1.Delineating genetic alterations for tumor progression in the MCF10A series of cell lines. 2.Identifying novel oncogenes and functional studies 3.Predicting clinical outcome using DNA methylation and gene expression signatures Part 1 Breast Cancer

5. Modified Wellings-Jensen Model of Breast Cancer Evolution

6. Breast Cancer Progression Models of the MCG10A Series of Cell Lines

7. DNA Copy Number Alterations in MCF10A Series of Cells Detected, Using Affymetrix 500K SNP Arrays

8. MCY Amplification in MCF10A Series of Cells Detected by DNA Copy Number Analysis Using SNP Arrays

9. CDKN2A/CDKN2B Deletions in MFC10A Series of Cells Detected by DNA Copy Number Analysis Using SNP Arrays

10. PIK3CA Mutation in MCF10CA1h and MCF10CA1a Cells

11. DNA Copy Number Alteratio ns in Primary Breast Tumors Detected with SNP Arrays

12. Focal Amplification Detected in Primary Breast Tumors

13. Focal Amplification of TBL1XR1 in Breast Tumors

14. Frequent Over-expression of TBL1KR1 in Primary Breast Tumors Using Tissue Microarray (TMA)

15. TBL1CR1-shRNA Knockdown in MCF10CA1h (M3) Suppresses in Vivo Tumor Growth

16. The PBCS included 2386 cases and 2502 controls They resided in Warsaw, Poland from 2000-2003 Median follow-up: 8 years 208 PBCS tumors with Illumina HumanRef-8 v2 Expression data 226 PBCS tumors with Illumina Human Methylation27 data In collaboration with Mark Sherman, Jonine Figueroa, Paul Meltzer, Sean Davis, and Melissa Troester The Polish Breast Cancer Study (PBCS)

17. An Algorithm for Methylation and Expression Index (MEI)

18. Polish dataset: K-M survival based on MEI

19. Polish dataset: K-M survival using MEI for ER+ and ER- samples

20. Validation: K-M survival using MEI for ER+ samples

21. 1.Microarray data analyses 2.Whole genome sequencing data analyses In collaboration with Phil Taylor, Nan Hu, Alisa Goldstein Part 2 Esophageal And Gastric Cancers

22. Clustering of ESCC and Gastric Cancers Using the Affymetrix U133 Gene Expression Data

23. Anatomy of Esophageal Cancer and Gastric Cancer

24. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma

25. A shared susceptibility locus in PLCE1 at 10q23 for gastic adenocarcinom a and esophageal squamous cell carcinoma

26. 4 pairs of ESCC and blood 4 pairs of gastric non-cardia cancer and blood 7 pairs of gastric cardia cancer and blood Analyses of Whole Genome Sequencing (WGS) Data Generated By The Complete Genomics Inc.

27. Circos Plot of WGS data from a Gastric Cardia Cancer: Somatic SVs, CNAs, and SNVs

28. Somatic Structural Variation s (SVs) in ESCC and Gastric Cancer

29. MACROD2 Exon 6 was Frequently Deleted in Gastric Cancer

30. Mutation Substitution Patterns 1

31. Mutation Substitution Patterns 2

32. Collaborators

33. Dr. Robert Wiltrout Dr. Glenn Merlino