How to remember which genes are tumor suppressors vs. proto-oncogenes

molecular neoplasiaHere’s a question that I got by email yesterday and it’s such a good one that I want to share it with everyone.

Q. I love love LOVE your blog and your daily emails, and your book “Clot or Bleed” saved my butt for studying for my hematology exam. I was just wondering – do you have a good mnemonic or know of an easy way to remember which cancer gene mutations are proto-oncogenes and which are tumor suppressors? Thanks so much!

A. Thanks for letting me know you found the book and other stuff helpful! I’m so glad to hear that.

I don’t have a mnemonic for these genes (if anyone does, please comment below!). I think the best way to remember these is to learn what each gene product does (because then you’ll know whether it’s a proto-oncogene or a tumor suppressor gene).

For example: RAS encodes a signal-transducing protein associated with cell growth. It takes the signal from a growth receptor, and helps get that signal down to the nucleus so something can be done about getting the cell to grow. So it’s a growth-promoting gene (a proto-oncogene). If RAS is going to be a cancer-causing gene (an oncogene), it is going to have to be mutated in such a way that it is always turned on.

Here’s another example: the retinoblastoma (RB) gene. The RB gene product inhibits the cell cycle, turning off normal cell growth when necessary. So it is a tumor suppressor gene (this is a dumb name, but we can save that tirade for another time). If you’re going to cause cancer by mutating the RB gene, you’d have to mutate it in such a way that it doesn’t work well (and cells can just whiz through the G1/S checkpoint no problem). And actually, kind of like the brakes on your car, you typically need to mutate BOTH alleles of a tumor suppressor gene in order to cause tumors (if you just mutate one allele, you’ll still have some “brakes” left in the other allele).

Here is my favorite diagram (above) relating to this topic. It’s from Robbins, and it’s got all the important cancer-related genes (or at least the most important ones for you to learn) listed according to what their products do in the cell. Yay! You can see RAS up there just beneath the cell membrane, doing its job as a signal transducer. RB is down in the nucleus, acting as a cell cycle inhibitor.

A nice touch in this diagram is the color coding: all the red things are growth-promoting (so their genes would belong to the proto-oncogene category). Blue things are growth-inhibiting (so they would be encoded by tumor suppressor genes). The green things function as DNA repair mechanisms (the nice little scissors and hammer). If you look at this diagram long enough, you’ll start remembering which color things are – and if you freak out on a test, remembering the color just might get you grounded again.

I am sure that someone does have a snazzy mnemonic. But I figure that since you’re going to have to learn what these gene products do, you might as well just reason out which ones are proto-oncogenes vs. tumor suppressor genes, rather than try to memorize that list separately using a mnemonic.

It’s always best when you can get material to make sense! Cuts waaayyy down on the brute memorization – and also helps get the info into long-term memory. Maybe save the mnemonic strategy for stuff that you can’t reason out, like cranial nerve numbers, or clinical syndromes that don’t make sense, or well, pretty much all of micro.

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