On page 188 Dr. Moalem mentions “more than 90 percent of the
cells in cancerous human tumors use telomerase.” However, several types of osteosarcoma (bone cancer) and soft
tissue sarcoma use alternative methods, such as the ALT-mechanism, to avoid
apoptosis.
Describe
the ALT-mechanism (or another alternative method) in terms of the manipulation
of genetic material during cell division. Then speculate on an evolutionary
advantage ALT provides for cancer in response to some environmental factor.
This
question relates to Big Idea 1 (the process of evolution drives the diversity
and unity of life) because several strains of cancer evolved an alternative
method of avoiding cell death in response to environmental factors, thus
contributing to the diversity of cancer.
Aidan
Murphy (amurphy4@students.d125.org)
This comment has been removed by the author.
ReplyDeleteAs Dr. Moalem says, under normal conditions, "without telomerase, cancer cells would die out after dividing fifty to sixty times" (188). However, thorugh ALT, which stands for alternative lenghtening of telomeres, telomerase is not needed to elongate the telomeres of cancerous cells. A journal article from the Human Molecular Genetics section of Oxford Journals describes one of the ways in which cancer cells can bypass the telomere-shortening safeguard that cells have in place.
ReplyDeleteOne mechanism for ALT is sister chromatid exchange (SCE). In a normal cell, sister chromatid exchange has no effect on the cell or its chromosomes since sister chromatids contain identical DNA nucleotide sequences, so when the same amounts of DNA at the same locations are transferred, the result is exactly the same as before the transfer. However, in certain cancerous cells, a mutation results in a much higher probability of unequal sister chromatid exchange in telomeric regions. Although the net amount of genetic material present is still the same, one chromatid experiences a major increase in telomere length while the other experiences a major decrease in telomere length. This is known as recombination of the telomeres.
Now, when this unequal chromatid pair divides, the sister chromatid with a shorter telomere region goes to one cell while the sister chromatid with a longer telomere region goes to the other cell. After one division, the cell with the longer telomere will divide into 2 cells, which lose a small amount of their telomere region but still have longer regions than the original. The shorter cell, after a few more divisions, quickly runs out of its telomere region and undergoes apoptosis. We can see that following telomeric recombination and then division of those unequal sister chromatids, one more normal cell division yields a total of 2 cells with longer telomeres and 2 cells that will eventually die off due to shorter telomeres. The net result is that the original cell underwent telomeric recombination and after two cell divisions ended up producing 2 cells with longer telomeres that will continue living on. In essence, one of the intermediate cells got "sacrificed," losing its telomere length, to prolong the life of the other cell.
ALT likely came about due to random chance rather than a certain environmental pressure. Telomerase requires a random mutation to be produced in cancerous cells just like a much higher chance of unequal sister chromatid exchange of telomeres requires a random mutation. Either way, these two mutations help the cancerous cell survive and created variation, connecting with Big Idea 1 (the process of evolution drives the diversity and unity of life). In fact, this could be seen as convergent evolution since two types of cancerous cells gained the same goal of telomere-lengthening through different means.
Austin Hua (auhua4@students.d125.org)
Source: http://hmg.oxfordjournals.org/content/14/suppl_2/R191.full