Maxwell Lee National Cancer Institute Center for Cancer Research High-dimension Data Analysis Group March 19, 2014 Integrated Studies Of Breast, Esophageal,

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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

Collaborators

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

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

Modified Wellings-Jensen Model of Breast Cancer Evolution

Breast Cancer Progression Models of the MCG10A Series of Cell Lines

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

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

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

PIK3CA Mutation in MCF10CA1h and MCF10CA1a Cells

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

Focal Amplification Detected in Primary Breast Tumors

Focal Amplification of TBL1XR1 in Breast Tumors

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

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

The PBCS included 2386 cases and 2502 controls They resided in Warsaw, Poland from 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)

An Algorithm for Methylation and Expression Index (MEI)

Polish dataset: K-M survival based on MEI

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

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

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

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

Anatomy of Esophageal Cancer and Gastric Cancer

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

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

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.

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

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

MACROD2 Exon 6 was Frequently Deleted in Gastric Cancer

Mutation Substitution Patterns 1

Mutation Substitution Patterns 2

Collaborators

Dr. Robert Wiltrout Dr. Glenn Merlino