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Transcript of Maxwell Lee National Cancer Institute Center for Cancer Research High-dimension Data Analysis Group...
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 2000-2003• Median follow-up: 8 years• 208 PBCS tumors with Illumina HumanRef-8 v2
Expression data• 226 PBCS tumors with Illumina Human
Methylation27 dataIn 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 Variations (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 WiltroutDr. Glenn Merlino