An article was recently published in Nature that looked at genome-wide differences between seven different prostate cancer tumors (link). The results are pretty amazing. The authors took advantage of massively parallel sequencing, which makes it possible to analyze entire human genomes in a fraction of the time that previous methods required. By looking at the whole genome at once, instead of individual genes as with the traditional approach, it becomes possible to see the proverbial forest among the trees.
By looking at the whole genome, the authors were able to see all the different kinds of mutations that were occurring in prostate tumor cells at once. This revealed the general types of mutations that were occurring. For one, it was found that a certain mutation that causes a DNA strand to be off by around 2 basepairs were fairly common in the tumor cells. Such mutations are also seen in breast cancer tumor cells, though they are much less common. In fact, the most common type of mutation seen in breast cancer tumor cells is not as common in the prostate cancer tumor cells. Considering that these are both cancerous tumors, this is somewhat surprising. They look and act in similar ways, yet internally they are quite different.
They also found that chromosomes were frequently rearranged in a variety of ways in the prostate cancer tumor cells. These rearrangements, although common, seemed to be a side effect of the cancer, instead of its cause. I say this because there was little pattern among the tumors; of the seven, there were seven very different patterns of chromosomal rearrangement. If prostate cancer is being caused by some DNA repair mechanism being turned off, then these results are to be expected. Such rearrangements may naturally occur by chance, but a cell with a functioning repair system would either be able to fix them, or destroy itself via apoptosis (sacrificing itself for the benefit of the person as a whole). Without such functioning repair mechanisms, such gross mutations would be able to occur with little bound.
While the rearrangements were seemingly random, certain genes were found to commonly be mutated. Some of these genes are very crucial to the proper functioning of the cell, namely histones. Histones wrap around DNA, and can prevent the genes in wrapped DNA from being expressed. Considering that all your cells are genetically identical, expressing all genes at once for a single cell is almost certainly detrimental. A liver cell is a liver cell because it expresses different genes than a lung cell. With the mutation of histones, however, gene expression can radically change. Cancer is a logical result of such a dramatic, mostly random change in gene expression. That said, I still think the histones are more of a side-effect, or perhaps a co-effect. They are at a deeper level than the chromosomal rearrangements, but I'm not sure if they are at the root of the cause.
The greatest take-home point of the paper is that prostate cancer is very unique. Given that the technology to make this study was only recently made available, there is a lacking of data on the genome-wide uniqueness of other cancer types. Personally, I would expect such studies on other tumor cell types to reveal more uniqueness. Even though cancer generally presents in the same sort of ways across all tumor types, this type of study shows that the similarities may be more superficial than we think. At a deeper level, there are great differences between the different kinds of cancers. A cure for breast cancer or prostate cancer may be possible, but a general, all-purpose cure for cancer may be far fetched. Although this isn't the positive message one may have hoped for, it does open new lines of inquiry. Besides this, it is helpful to know that these things are more different than they appear, lest we spend resources unnecessarily to find a general cure that can't possibly exist.
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