Aberrant Chromosomal Rearrangements in Cancer
Posted on | December 29, 2008 | 1 Comment
Chromosomal Rearrangements (adopted from Hampton, Hollander, Miller et al. 2008)
Yesterday, I was just browsing through the internet and stumbled upon a really interesting article called “The Chaos Inside a Cancer Cell” in New York Times in the science section. Naturally, it grabbed my attention because of my immediate interests in cancer genetics but the article was just a brief overview with very few details so I decided to venture a bit deeper and dug up the actual article from Pubmed. It is available for free so everybody can view it if you so decide.
Now, obviously the reason I am writing this post is to let you in on some of the details of this beautiful paper and spare you some of the complexities. On that note, let me get started. The article explores genomic aberrations in MCF-7 breast cancer cell line derived from a 69-year old Caucasian woman in 1970 who underwent two mastectomies. Many researchers choose this cell line because it has been very extensively researched and documented upon, making it a good research model.
As you may know, one of the common characteristics of a cancer cell is its uncanny ability to survive. ‘Normal’ cells have a biological clock and they have a mechanism to self-destruct called apoptosis. But cancer cells do NOT. Additionally, if DNA breaks or damaged DNA are not corrected, it is often a signal for the cell to kill itself but cancer cells can surpass that checkpoint. It is also pretty widely accepted now that chromosomal instability leads to tumorigenesis. These are basically genetic mutations that either enhance cell survival or proliferation. In all, it makes studying cancer genomes of obvious interest relative to normal genomes to understand their unique survival and/or proliferative advantage.
Hampton and his colleagues at Baylor College of Medicine did exactly that by studying genomic changes in MCF-7s. The picture above is taken directly from their article not only because of its aesthetic appeal but also because it contains a lot of key data and should suffice in conveying what I want to through this article. The circle on the outside shows all 23 of human chromosomes. The second circle with green and red is out of the scope of this article so we won’t talk about it. Most of the interesting data is in the blue lines, which show rearrangement within the same chromosome (intrachromosomal), and red lines which depict rearrangements between different chromosomes (interchromosomal). As you can see, there are a lot of changes and switching over of genetic material going on, which in this case is not a good thing and you will see why if you read on.
But for now if you focus on the density of blue and red lines you will notice that these chromosomal rearrangements seem to be clustered, whether it is intrachromosomally or interchromosomally. For example, look at the amount of red between chromosomes 1, 17, and 21 as opposed to the rest. Hampton et al. refer to these rearrangements as clustered and the others as dispersed. Simply put, clustering probably somehow affects DNA repair negatively and therefore generates more genomic instability leading to more tumor potential.
The above data begs to be asked why all these rearrangements are bad. And the answer is contained in the genes that are affected by these massive amounts of rearrangements. Because of these changes, some genes are ‘inactivated’ in a way and a few that were screened, in fact, were either tumor suppressors or provided genomic stability. In other words, cancer cells are suppressing expression of genes that make up the correction/stabilization machinery of the cell.
In summary, Hampton et al. have shown that genomic rearrangements in cancers both lead to structural changes causing genomic instability and additionally have a mechanistic impact by further suppressing genes that would cause it to become uncancerous.
References:
Hampton, Hollander, Miller et al. (2008) A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yield insights into the evolution of a cancer genome. Genome Res
Comments
One Response to “Aberrant Chromosomal Rearrangements in Cancer”
Leave a Reply
February 9th, 2010 @ 21:16
Hello everybody! I do not know where to start but hope this site will be useful for me.
I will be happy to receive any assistance at the beginning.
Thanks in advance and good luck!