Monday, December 19, 2005

The NIH’s Cancer Genomics Project

In a move that you either view as ambitious (if you are a geneticists) or misguided (if you are a cell biologist) the NIH has unveiled a cancer genomics project. Nature reports the two perspectives:

“The project is a potentially huge undertaking that could take 10 years and cost US$1.5 billion. Its proponents say that tallying up all the genetic mutations in cancer cells may reveal new drug targets.

“But opponents argue that cancer biology is too poorly understood to make such a cataloguing approach viable and say that the money would be better spent on basic research into how cancer functions.”

The project will consist of the following steps:

  1. Sample two or three types of tumors from multiple individuals (I’m guessing on the orders of hundreds or thousands of cancer patients).
  2. Perform “high-throughput” analysis on the cells -- the Nature article indicates gene expression as one type of analysis, but does not describe any others. Maybe Orac knows of some other analyses.
  3. Sequencing of about 2,000 genes from each of the tumors. How will the researchers choose these genes? I have no idea, and I don’t know if the heads of this project know.

A Washington Post article describes the different genetic causes of cancer, something the Nature article fails to do:

“Some cancers are caused by a mutation in a single gene that normally keeps a cell from making offspring. Others are caused by the mistaken duplication of a gene that promotes normal cell division, boosting its reproductive capacity to abnormal levels.

“In other cases, entire pieces of chromosomes -- long, gene-bearing strands of DNA inside cells -- break off and reattach to other chromosomes, inducing spurious and unregulated growth signals.

“Still other cancers result when rogue molecules attach themselves to genes whose job is to control cell division. Such “epigenetic” changes are invisible on standard tests that look for mutated genes because the genes themselves are healthy but are being manhandled by the other molecules.”

From the brief descriptions of the project I have been able to find, the proposed NIH research plan will only deal with mutations in single genes. Unless the “high-throughput” analyses that go unnamed consist of karyotyping or in situ probes for duplications, this study won’t even skim the surface of the genetics of cancer. I don’t think you can even do either of these in a high-throughput manner. The epigenetic effects may be picked up by the gene expression analysis, but it will be difficult to distinguish between mutations to regulatory regions (cis effects), mutations to transcription factors that control the expression of the gene (trans effects), and epigenetic effects.

Without more detail, it’s hard to judge the merits of this project. The research will definitely result in some worthwhile discoveries, but it may be wiser to spend the money on more detailed analyses. Just because “high-throughput” works for genome sequencing, doesn’t mean that Francis Collins needs to apply it to every study the National Human Genome Research Institute gets involved in.


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