TCGA gene expression data are missing matched normal

Question

I'm trying to use the TCGA data portal to get gene expression data for cancer tissues, but I'm not sure what "Tumor matched normal" means.

It is unclear to me if the values are already compared to a control (non cancerous) tissue or there is another sample which gives the healthy tissue values. Assuming it is the latter, I don't see these samples anywhere.

This is a screenshot of my filter

http://www.clipular.com/c/5452873408184320.png?k=rlA9jy3Kb2U47JT7GrXBTzdsln4

And here is a picture of the result (only TNs appear).

Answer 1

These values are not already normalised to normal tissue controls. That a tumour is marked as tumour with matched normal doesn't mean that all of the platforms used by the TCGA (Expression, CNV, protein and methylation) have normal tissues available - in most cases Tumours with Matched Normals are annotated thusly because mutation calling was performed using tumour vs normal comparisons.

If you are looking for normal tissue controls for your given platform type (RPPA in your screenshot) you will find them labelled NT or N. If you don't see any that are labelled with those descriptions it means normal tissue samples have not been processed using that platform.

The TCGA doesn't do loads of normal tissue analysis for anything other than mutation calling because the project is focused on classifying tumours into subgroups using unsupervised approaches, primarily, and therefore all comparisons that get heavily used are tumour vs tumour after allocation to subtypes.

Answer 2

The TCGA Project has been collecting primary tumors and matched normals per patient per cancer indication and has been exome (WXS) profiling those samples, and genome (WGS) profiling a subset of them. In those cases, the primary tumor is tissue collected from the primary tumor and the matched normal is usually a blood samples, but could be derived from a buccal swab or some other source. As you can imagine, it would make less sense in terms of expression to assay matched control that derives from another tissue type such as blood.

For the expression data, the majority of the data comes from RNA-Seq and array-based profiling of the primary tumor data, and in some cases where adjacent normal tissue was collected and submitted, the TCGA has also profiled those samples. These are probably what you are seeing with your TN filter, and generally why you are having trouble finding equivalent amounts of matched normals as compared to primary tumor samples for the expression projects.

Incidentally, the company I work for has recently launched a free genomics data portal for the research community called GeenPool Reference. As part of it, we have deposited all of the publicly available TCGA RNA-Seq. The data along with all the associated clinical metadata is readily available for navigating and data mining. You'll easily be able to figure out the quantity of samples, and their matched pairs. If you're interested, you can take a look at the data projects available in GenePool Reference here: http://www.stationxinc.com/reference-library

~Sandeep