Oncogenic mutations?

Stephen Gisselbrecht gisselbr at husc8.harvard.edu
Mon Apr 26 16:59:45 EST 1993

In article <6849 at krafla.rhi.hi.is> agnar at rhi.hi.is (Agnar Sturla Helgason) writes:
>oncogenic mutations are always dominant, while tumor 
>suppressor gene (anti-oncogenic) mutations are always reccesive. Another 
>reference seems to indicate the possibility of recessive oncogenic mutations 
>(this could be a misunderstanding on my behalf). 
>Can an oncogenic mutation be reccesive? And if not, why?
>                                  Agnar Helgason, Iceland.

	If you think of cancer as simply the state of uncontrolled cell
growth (a simplification, but an acceptable one for purposes of this 
discussion), then there are two basic classes of mutations that will lead to
cancer.  The first causes what's normally an inducible signal to grow to be
sent continuously--these mutated genes, which constantly tell the cell to
grow, are referred to as oncogenes.  Since the product of the oncogene is
sending its growth signal whether or not the wild-type gene product is
also present, these mutations are generally dominant.
	The second kind of mutation that contributes to cancer causes the
inactivation of a signal that suppresses growth.  The genes that this
kind of mutational event effect are called tumor suppressor genes or, less
frequently, anti-oncogenes.  Here is the source of the confusion--an
inactivating mutation in an "anti-oncogene" is not an "anti-oncogenic"
mutation; it is a mutation that can contribute to the rise of cancer, and
thus it is also an oncogenic (from Greek words for "giving rise to
cancer") mutation.  Because it is usually the case that the single
remaining wild-type copy of the gene can continue to send its growth
suppressing signal despite the inactivation of one copy, these mutations
are generally recessive.

	I hope that that helped to clear things up (and that I haven't
insulted your intelligence by pitching my explanation too low!).

					steve gisselbrecht
					cell & dev. bio.
					harvard medical school

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