# Presentation: 831365

## The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- Transcriptional information on GBM from TCGA pilot projectTranscriptional subsets
- Integrative approaches and opportunities

- _Transcription teams_**Broad Institute of MIT and Harvard.**** **Affymetrix U133A platform
**Lawrence Berkeley National Laboratory and UC Berkeley.**  Affymetrix Exon 1.0 platform.
**University of North Carolina.  **Agilent array platform**Johns Hopkins University and University of Southern California. **Illumina Genotyping platform to detect changes in methylation

## The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- Transcriptional information on GBM from TCGA pilot projectTranscriptional subsets
- Integrative approaches and opportunities

## Consensus clusters

## Comparison of Groupings by Gene Expression and microRNA

|  | Gene Expression |  |  |  |
| --- | --- | --- | --- | --- |
| microRNA | 1 | 2 | 3 | 4 |
| 1 | 2 | 8 | 11 | 12 |
| 2 | 14 | 12 | 8 | 10 |

## Alternative Transcript Subgroups  Using Exon Arrays

- Alternative Transcript Subgroups  Using Exon Arrays

- Gene Models

- Distance along gene

- Transcript measurement

## Statistical Approaches to Finding Splicing Isoforms

- Statistical Approaches to Finding Splicing Isoforms

- exons

- FIRMA  - ***F***inding ***I***soforms using
***R***obust ***M***ultichip ***A***veraging

-  E. Purdom, T. Speed,

## The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- Transcriptional information on GBM from TCGA pilot projectTranscriptional subsets
- Integrative insights

## EGFR Deletions in GBM Samples

- EGFR** **Deletions in GBM Samples

## EGFR C-terminal Deletions are Functional 

- EGFR C-terminal Deletions are Functional

- Wild-type EGFR

- C-terminal EGFR deletions are biochemically active without added EGF

- WT

- CT997

- CT1009

- Vector

- EGF (20ng/ml)     -        +       -        +       -       +        -       +                              (5 min)

- WT EGFR

- CT truncated EGFR

- P-STAT3 (Y705)

- STAT3

- CT997 deletion

- CT1009 deletion

- Cho, Jeonghee

- Jeonghee Cho
- Matthew Meyerson

- Increased NIH-3T3 cell colony formation in soft agar

## DNA Polymorphisms Influence Exon Level Expression Measurements

- DNA Polymorphisms Influence Exon Level Expression Measurements

- exon

**SNP**
**(AvHet=0.39)**

***OAS1***;   2',5'-oligoadenylate synthetase 1

- Samples

## Mutation Mediated Transcription

- Mutation Mediated Transcription

- Abnormal FIRMA score

- P53 Mutation detected

- Exon array probe

- Sample

- Transcript lost due to nonsense mediated degradation caused by premature termination codon?

- A. Lapuk and the TCGA

- Note:  Not yet validated experimentally

## DNA Hypermethylation vs. Transcription

- DNA Hypermethylation vs. Transcription

- Laird, Schuebel, Herman, Cope and the TCGA

## The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- The NCI-NHGRI Cancer Genome Atlas (TCGA) Pilot Project

- Transcriptional information on GBM from TCGA pilot project

- _Transcription teams_
**Broad Institute of MIT and Harvard.  **G. Getz, W. Winkler, R. Verhaak, D. Chiang, M. Meyerson
**Lawrence Berkeley National Laboratory and UC Berkeley.**  A. Ray, S. Durinck, V. Wang, E. Purdom, T. Speed,  A. Lapuk, P. Spellman, J. Gray
**University of North Carolina.  **V. Weigman, Y. Qi, N. Hayes, C. Perou **Johns Hopkins University and University of Southern California.  **P. Laird, L. Cope, K. Schuebel, J. Herman, S. Baylin