Overturning Ideas on Cancer

Another advance in cancer research is featured on our website this week. Among other things, this one highlights the dangers of assuming causation from correlation. Prof. Dov Zipori and his team were looking at adult stem cells in the bone marrow. These hold a lot of potential for treating many kinds of disease but, like many kinds of stem cells, there is a risk of these cells differentiating into cancer instead of the intended normal tissue replacement. The idea was to find a marker that could tell which cells were more likely to turn cancerous, thus making the use of these stem cells safer.

Zipori1
Polyploidy in an adult stem cell. From the lab of Prof. Dov Zipori

What the team discovered – to their great surprise – is that a major change in chromosome number that has been associated with cancer is actually found in stem cells that are less likely to become cancerous. This change is called polyploidy: a multiplication of the entire set of chromosomes such that three, four or even more sets appear in the adult stem cells. Up to now, it has been obvious to everyone that the excess chromosomes in polyploidy can lead to the excess growth of cancer.

When the facts tell a different story, the explanation must change as well, and Zipori has an explanation: Polyploidy may be a cell’s way of avoiding cancer. Adding more genes can dilute the effect of a potentially harmful mutation in one. The fact that some cancer cells are polyploid simply means that the strategy doesn’t always work.

This insight, by the way, led Zipori and his team to a gene that is about a thousand times more active in diploid than polyploid cells. The analysis of this gene turns out to be a good predictor of cancer risk in adult stem cells.

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Why exactly is this a surprise..?

At least as a superficial analysis.. at least some of the mutations that lead to cancer will involve genes becoming broken (some may involve over-expression which polyplody will not help much). If you have 4 copies of a gene then it requires 4 mutations to completely remove the functionality, which is exponentially harder than 2.

Furthermore, it becomes that much harder to knock out the apotosis mechanisms.

Obviously, there would be side effects.. but if an organism could be engineered for quardroploiy, surely the cancer rate would be lower.

By Andrew Dodds (not verified) on 04 Mar 2013 #permalink

It is a surprise exactly because polyploidy has been associated with cancer. And it is a somewhat risky strategy, because doubling chromosomes with certain mutations could accelerate the cancer process, rather than inhibit it.