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Loyola Marymount University Exploring Comprehensive Gene Expression Analysis of Prostate Cancer Reveals Distinct Transcriptional Programs Associated With Metastatic Disease Through GenMAPP & MappFinder LaTulippe Eva, Satagopan Jaya, Smith Alex, Scher Howard, Scardino Peter, Reuter Victor, and William G. Cancer Research 2002 Aug 1; 62, 4499-4506. Kevin Paiz-Ramirez Janelle N. Ruiz Biology 398.01 Department of Biology Loyola Marymount University April 21, 2010

Outline

Previous Studies Explored Function of Unknown Genes May Identify Potential Therapeutic Targets La Tullippe et at. used high-throughput gene expression analysis to study prostate cancer metastasis Differentially expressed genes between metastatic and primary tumors were found in: Cell Cycle Regulation Mitosis Signaling DNA Replication Metastatic tumors had higher proliferation index than primary tumors. Took out resutls slide (can discuss with figures – this info not so relevant to presentation of reuslts) Expression of genes corresponding to 5992 probe sets were reliably detected in all 23 primary prostate carcinomas 22665 did not detect expression in any of the samples 9 of 23 primary sample patients experienced a recurrence. 132 were over-expressed in primary tumors and 360 in metastasis 3

Genome Wide Expression Analysis of Primary and Metastatic Prostate Cancers Tissues samples were taken from: 3 Non cancerous Patients 23 Primary Prostate Cancer Patients 9 Metastatic Prostate cancer Patients Collected as biopsies from 1993-1999 Genes were considered to be differentially expressed if they differed by 3 fold between two groups

Running GenMAPP & MAPPfinder The Log2 of the ratio of the means was calculated: H vs PG fold Met vs PG Fold H vs Met Fold AI vs PG Fold Number of errors 1793/11977 Z score > 2 PermuteP <0.05 Number of genes not found in the database, ids based off of affymetric genes, control genes on the chips, not human genes. A range of greater than or less that where we chose. The low and high for the comparisons.

Increased & Decreased Results of H vs. PG Fold Cut off header and split to two slides Decrease Increase

Increased and Decreased Results of H vs.PG Fold Decreases centered on: Nucleosome activity Chromatin activity Chromosomal activity DNA packaging Increases centered on: Activation of MAPK activity Leukocyte chemotaxis Metanephros development Immune response

Increased & Decreased Results of Met vs. PG Fold

Increased and Decreased Results of Met vs.PG Fold Increases centered on: Mitosis Spindle organization Chromosome segregation DNA replication Decreases centered on: Muscle contraction Chromatin remodeling complex Oxidoreductase activity