What is the difference between 17p deletion and TP 53 mutation?

[ivy39]

I read about both occurrences but can never fully understand the difference. For example: is TP 53 a protein or another gene?

[Newdawn Administrator]

I'm not sure if you'd read this Ivy but hopefully it will help;

cll-nhl.com/2012/10/17p-del...

Newdawn

[ivy39 in reply to Newdawn]

Thanks Newdawn. I did read Dr. Sharman's blog but am still unclear as to the distinction between 17p- and TP53 deletion.

[Cllcanada Top Poster CURE Hero in reply to ivy39]

The exact location on chromosone 17 is 17p13.1... at this location resides the TP53 gene, that encodes the p53 protein...

If there is a deletion, a piece missing the TP53 gene on that arm is damaged...

However, we have two arms in chromosomes, and two TP53 genes, but they remaining one is often mutated.

However, you can not have any danage to chromosome 17 but still have a mutaed or non-functional TP53 gene.

So there are two different scenarios, a missing chromosone and a second damaged one... or a mutated or nonfunctional TP53 gene on one allele or arm.

Interestingly, elephants have 20 TP53 genes, they rarely if ever get cancers.

elifesciences.org/content/5...

~chris

Here is Dr. Leclair's bit..

Note that the gene used to be called p53, it has changed now to TP53 and the protein it enclodes is now p53... 😩

patientpower.info/what-exac...

[ivy39 in reply to Cllcanada]

Thanks Chris. So you can have both alleles of chromosome 17 (i.e. no deletion) but still be in trouble because the gene TP53 on either or both allele(s) could be damaged or absent and hence render the gene incapable of activating the protein TP53 which normally acts as a cancer antigen or "the guardian of the genome"?

[Cllcanada Top Poster CURE Hero in reply to ivy39]

According to Dr. Keating in a video recently, you can not have a double 17p deletion, on both alleles, the cell is not viable. I think the same would apply to two defective TP53 genes.

You can however have double deletions on 11q and 13q, something that causes genetic instability ... and in the case of 11q a fairly agressive clinical course... in the 11q situation the missing gene is ATM... it is TP53s quality control inspector in the cell clone cycle.

As you can image with no quality control..a lot of bad cells are going down the assembly line...

~chris

[mesmer]

There is a whole book about this gene: P53, the Gene that Cracked the Cancer Code by Sue Armstrong. p53 is the gene and genes code for proteins. Genes are like the recipe manual for making the proteins and the genes sit on chromosomes. p53 happens to sit on chromosome 17, the top arm of it. All chromosomes (except the male Y chromosome) have a short arm (p) and a long arm (q). Why p? It's French for petite. Then why q for the long arm? Because q comes after p in the alphabet. The reason really is that stupid.

Scientists use a certain notation to differentiate genes and proteins: the gene gets italicized, but the gene product, i.e., the protein, is written without italics. I mention this in case you see p53 and p53. (The first is the protein, the second, in italics, is the gene.) However, outside of scientific journals, writers probably don't italicize the gene to distinguish it from the protein.

Why 53? Again, scientists sometimes lack imagination. The protein has a size of 53 kDa (53,000 Daltons). Daltons is the unit used for measuring protein mass. Many people are familiar with insulin, so for comparison, we can mention that Insulin is a little protein, 8000 Daltons. p53 is an average-sized protein, 53,000 Daltons. Antibodies (also called immunoglobulins) are big proteins, around 150,000 Daltons. But big is relative: individual protein molecules are way too small to be seen in a microscope. If a cell is a cat, then the antibodies are like fleas on the cat, to use AussieNeel's metaphor from a few days ago.

Now comes the unusual part of the story. When p53 was first discovered (1980), it was believed to be an oncogene, a gene that CAUSES cancer. It turns out, this was a mistake, because the scientists had accidentally chosen to study a p53 that was mutated, and mutated is bad. It leads to cancer. To make a long story short, it took some years until they realized the mistake. So now, instead of p53 being an ONCOGENE, it is recognized to be a TUMOR SUPRESSOR gene. So that's where the T in TP53 comes from (T for tumor). TP53, Tp53, p53 all refer to the same protein produced by the gene p53; different laboratories worked on it at the same time and gave it slightly different names. Here's the whole story: ncbi.nlm.nih.gov/pmc/articl...

And if you managed to read this far without falling asleep, congratulations!

[ivy39]

A most informative and clear explanation. Thank you!