Dr. Chris Pelloski presented his analysis of methylation status in glioblastoma at the American Association for Cancer Research "Molecular Diagnostics in Cancer Therapeutic Development" meeting being held at the moment. AACR made a press release that you can see here:

Methylation levels key to glioblastoma survival

Quote:
"This study shows that the methylation status of CpG islands may serve a robust, and previously unexplored, source of biomarkers for this disease," said lead author Christopher E. Pelloski, M.D., an assistant professor of radiation oncology and pathology at M. D. Anderson. "It also indicates that there seems to be a common theme to glioblastoma that the more closely the tumor cells resemble cells of neural development, the less aggressive the clinical course; whereas if they more resemble mesenchymal cells, which are poorly differentiated and invasive, the worse the clinical outcome will be.

A nice comprehensive blog post on the TCGA brain study can be seen here:
http://www.highlighthealth.com/diseases-and-conditions/the-cancer-genome-atlas-reports-molecular-characterization-of-brain-tumors/trackback/

It is interesting how the perception of TCGA has changed - it is hard to remember that there was a time when some people were very concerned about whether it would yield anything of value. The blogger at highlighthealth.com says:

"This is an excellent example of how current genome characterization technologies can systematically explore the universe of genomic changes involved in cancer. The TCGA is also studying lung and ovarian cancer."

Pablo Freire, working with Dr. Jonas Almeida on the TCGA data, has posted new data to our (secure) TCGA intranet site. If you are part of our MDACC TCGA group and wish to have access to these data, please send an email to Oliver Bogler.

Pablo writes:

The data is presented as tab-delimited files and can be imported to excel. For the expression and copy number data, those values are calculated for every affymetrix probe position. Sequence data are the exact tab-delimited files from the TCGA portal.

For the expression and copy number files, I did the following:

Expression platform: Affymetrix U133A plate set, performed by Broad Inst.
Copy number platoform: Agilent 244A aCGH, performed by Harvard Medical School.

For expression, the raw data (CEL files) were retieved from the TCGA portal. For the copy number, the normalized data was used.

Expression data normalized with RMA.
Copy number data segmented with CBS.

For every affymetrix probe position, I eliminated genes that were not annotated at the RefSeq or probes that either don't match anywhere or match in more than one location in the genome.
Also, for every affymetrix probe position, I calculated the copy numeber associated by getting the mean values of the copy number probes within the span of the gene.

Just one sample per patient was used. In the cases where there were multiple samples per patient, the first one was used, yielding a total of 207 patients.

Links to the data are (access & password required):

TCGA sequence data

TCGA Agilent copy number

TCGA Affymetrix Expression

The first TCGA paper was electronically published today by Nature:

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

The Cancer Genome Atlas Research Network

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

Comprehensive genomic characterization defines human glioblastoma genes and core pathways : Abstract : Nature

You can download a pdf proof version at that site.

According to the GeneGo website:

"MD ANDERSON BECOMES A GENEGO CENTER OF EXCELLENCE USING METACORE FOR ONCOLOGY RESEARCH

St. Joseph, MI. September 2nd, 2008 - GeneGo, Inc., the leading systems biology tools company, announced today that MD Anderson has become a certified GeneGo Center of Excellence. MD Anderson researchers will have institution-wide access to GeneGo's MetaCore data analysis suite, training and advanced support. MD Anderson specializes in cancer treatment and research and is well known for its advanced clinical trials programs. MetaCore will be used throughout many research programs both as a central data repository, management and collaboration platform for clinical OMICs data and as an integrative pathway analysis suite.

Mary E. Edgerton, a pathologist performing cancer research at MD Anderson and a long-term client, says "I have been using Metacore for many years in my research into pathways and networks that control aggressive behavior in cancers. I am currently using it to infer networks from analysis of gene expression array data for pathways in lung, brain, and breast cancer. I also use the curated pathways to formulate mathematical models of molecular networks that predict tumor behavior using multiscale modeling. Not only do I find the product to be very useful, but I also appreciate the responsiveness of the staff at Genego to my technical questions and suggestions."

"MD Anderson is renowned for their pioneering work in oncology, I have known some of the MDs there for a while and I admire their dedication to their patients and to working hard to find cures." said Julie Bryant, GeneGo's VP of Business development. "We are proud to have them as an institution customer and a Center of Excellence. We have a large development program in the area of cancer system biology tools supported by NCI and we are glad to see this work appreciated by some of the best oncology professionals in the world working at MD Anderson.""

GeneGo, Inc. Systems Biology for Drug Discovery

How can we all get into the GeneGo action? Anybody tried it yet? Please comment below.

A very interesting lecture by computer scientist, and thinker, David Levy, given at Google in March, 2008.

It discusses different modes of thought, and how the most important thinking is hard to do in our ever accelerating culture. Important viewing for us all, as we grapple with large problems that require good thought. Cultural acceleration has been with us longer than you might think...

And, since YouTube is no longer blocked, you should be able to see it:

YouTube - No Time to Think