Tag Archives: mutation

Hallmarks of Cancer 7: Genome Instability and Mutation

Mutation-Rates2

Here is the 7th installment from Dr. Buddhini Samarasinghe‘s article series on the Hallmarks of Cancer. You can read the full article on Scientific American. Here’s a snippet. Please go check it out. She has a wonderful knack of making very complex bioscience topics understandable. Here’s a snippet, please check out the full post.

Mutations 101
Mutations enable cancer cells to embark on their frenzied growth within our bodies. But what are mutations, and how do they happen? In genetics, a mutation is a change in an organism’s DNA sequence. The nucleotide letters A, T, C and G that make up our DNA can be deleted or substituted, and single or double stranded breaks can occur in the DNA molecule. Complete sections of our DNA can also be deleted or swapped with other sections. These changes can occur spontaneously or from exposure to inducers such as harmful chemicals or radiation. Our metabolic activities cause mutations all the time; oxygen, the vital molecule that helps us live, also creates dangerous DNA-damaging free radicals when metabolized by our cells. A sunny day at the beach can introduce thousands of mutations into our DNA. In fact, mutations are inevitable; each time our cells divide, the imperfect DNA replication process introduces temporary errors into our DNA. It has been estimated that all these processes can result in thousands of individual molecular lesions per cell per day. Our genome surveillance system and DNA repair mechanisms must be doing a fantastic job: based on these mutation rates, cancer should occur from the moment we are conceived.

Please go back and check out her other posts. They’re worth your time.

17p Deletion in CLL

karyotypeRe-Blogging something I found yesterday which helps explain small arm 17p deletion; the chromosomal mutation I have which makes my CLL more sinister. Dr Sharman helps explain it well and explains why traditional chemotherapy regimens like FCR (Fludarabine,Cyclophosphamide & Rituxan) for CLL generally don’t work well for patients w/ 17p deletion.. Thanksfully, Ibrutinib is well on its way to approval by the FDA and the trial drug I am taking (ipi-145) also seems to be working for me. Here’s a snippet of his post. You can read his full post via Dr. Sharman’s CLL & Lymphoma Blog

When we say 17p deletion CLL, what we mean is that the short (petit) arm of chromosome 17 is missing.  You have 23 pairs of chromosomes (46 total) and as you get higher in the numbering, the chromosomes get smaller and smaller.  It is probably an excessive simplification to say that the biology of 17p is all about one particular protein called p53 – but for the time being that is most of the story.

P53 is affectionately called “the guardian of the genome.”  Every time I read about p53 I discover some new function of the protein that I didn’t know about before.  It has a tremendous number of different functions.  One of the most important though is that it will bind to DNA in a bunch of places and turn on / off the genes at those locations.  In this role it is known as a “transcription factor.”  Many of the proteins that are regulated by p53 have to do with cell survival or cell death.  When P53 decides it is time for a cell to die – very few things can stop that.  The most important signal that turns on p53 is DNA damage (hence – guardian of the genome).