USMLE why is protooncogene "dominant"?

[ketap]

hi, i need help , please...i am very weak at genetics and really need some advice..i am quiet confuse.. why is protooncogene only need one mutation to cause tumor and why is tumor suppressor need two?

just to help if i am not describing it well enough.. i quote it from stanford website:

"Having a mutation in just one of the two copies of a particular proto-oncogene is enough to cause a change in cell growth and the formation of a tumor. For this reason, oncogenes are said to be "dominant" at the cellular level.

and
Both copies of a specific tumor suppressor need to be mutated (both members of the gene pair) in order to cause a change in cell growth and tumor formation to occur. For this reason, tumor suppressor genes are said to be "recessive" at the cellular level."

many thanks, Ketap

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[mcloaf]

An oncogene is oncogenic when it is present, a tumor suppressor is oncogenic when it is absent. It only takes one mutation of a proto-oncogene for it to start producing its oncogenic protein product and be an oncogene (a gain of function mutation). Thus the oncogenic mutated allele is dominant. If you knock out one copy of a tumor suppressor (loss of function) you still have the other copy producing enough functional product to inhibit oncogenesis, so it is not until both copies are mutated that cancer starts which is why you would say that tumor suppressor mutations are recessive.

This is a more thorough presentation: http://biochemistry.ucsf.edu/programs/ptf/m3 links/TumorSuppressLEC.pdf

 

[ulikedaggers]

An oncogene is oncogenic when it is present, a tumor suppressor is oncogenic when it is absent. It only takes one mutation of a proto-oncogene for it to start producing its oncogenic protein product and be an oncogene (a gain of function mutation). Thus the oncogenic mutated allele is dominant. If you knock out one copy of a tumor suppressor (loss of function) you still have the other copy producing enough functional product to inhibit oncogenesis, so it is not until both copies are mutated that cancer starts which is why you would say that tumor suppressor mutations are recessive.

This is a more thorough presentation: http://biochemistry.ucsf.edu/programs/ptf/m3 links/TumorSuppressLEC.pdf

Yup. Though some will say that tumor suppressors are dominant since it's likely that in any given cell there will be a mutation in the normal allele and cause that cell line to become cancerous (two hit hypothesis)

 

[Ionian]

Also memorize this:

AD Inheritance is always associated with expression of the trait, in the case of tumor suppressor gene mutations, the trait is the increased risk of developing cancer. Because Inheritance of a single defective genes increases the risk for tumor development, and under the proper conditions cancer may occur in 100% of carriers, the pattern of inheritance is characteristically: Autosomal dominant, with reduced penetrance. It has also been coined the “Dominant effect of a recessive mutation”.

 

[notbobtrustme]

With cell turnover rates, it's almost guaranteed that proto-oncogenes will get knocked out in any given cell line. However, since most people have 2 copies, this doesn't become a problem. When a person starts the game off with a broken copy of XYZ gene, then the chances of a knockout occurring in that same gene is extremely high, giving a dominant expression, even though genetically, you need both genes knocked out.

 

[CodeRedDew]

With cell turnover rates, it's almost guaranteed that proto-oncogenes will get knocked out in any given cell line. However, since most people have 2 copies, this doesn't become a problem. When a person starts the game off with a broken copy of XYZ gene, then the chances of a knockout occurring in that same gene is extremely high, giving a dominant expression, even though genetically, you need both genes knocked out.

proto-oncogene? I think you mean tumor-supressor gene.

 

[notbobtrustme]

proto-oncogene? I think you mean tumor-supressor gene.

goddamnit, I always get the two mixed up

 

[Bear Grylls]

goddamnit, I always get the two mixed up

Tumor suppressor gene = recessive, example is retinoblastoma

Proto oncogene = dominant, example is BRCA

 

[ketap]

thanks,Friends ..

Also memorize this:

AD Inheritance is always associated with expression of the trait, in the case of tumor suppressor gene mutations, the trait is the increased risk of developing cancer. Because Inheritance of a single defective genes increases the risk for tumor development, and under the proper conditions cancer may occur in 100% of carriers, the pattern of inheritance is characteristically: Autosomal dominant, with reduced penetrance. It has also been coined the “Dominant effect of a recessive mutation”.

hi, Ionian..sorry, but i don't get what you mean..would you please explain it to me again..thx

 

[Ionian]

Tumor suppressor gene = recessive, example is retinoblastoma

Proto oncogene = dominant, example is BRCA

I don't think Tumor suppressor gene mutations are not "recessive" by any means of the definition.

The genetic inheritance for either category is autosomal dominant.
If it was recessive, a person who inherited only 1 defective RB (lost only 1 copy) would NEVER express the trait/cancer (they would just be a carrier), this is however not the case (esp when they show you the pedigree it becomes clear you shouldnt pick recessive), the second allele can be very easily lost, especially under the appropriate conditions.

This is clearer in robbins then in the one-liner simplification in FA.

Again:
AD Inheritance is always associated with expression of the trait, in the case of tumor suppressor gene mutations, the trait is the increased risk of developing cancer. Because Inheritance of a single defective genes increases the risk for tumor development, and under the proper conditions cancer may occur in 100% of carriers, the pattern of inheritance is characteristically: Autosomal dominant, with reduced penetrance. It has also been coined the “Dominant effect of a 'recessive' mutation”.

Tumor suppressor genes are inherited in a dominant fashion.

 

[sanj238]

I don't think Tumor suppressor gene mutations are not "recessive" by any means of the definition.

The genetic inheritance for either category is autosomal dominant.
If it was recessive, a person who inherited only 1 defective RB (lost only 1 copy) would NEVER express the trait/cancer (they would just be a carrier), this is however not the case (esp when they show you the pedigree it becomes clear you shouldnt pick recessive), the second allele can be very easily lost, especially under the appropriate conditions.

This is clearer in robbins then in the one-liner simplification in FA.

Again:
AD Inheritance is always associated with expression of the trait, in the case of tumor suppressor gene mutations, the trait is the increased risk of developing cancer. Because Inheritance of a single defective genes increases the risk for tumor development, and under the proper conditions cancer may occur in 100% of carriers, the pattern of inheritance is characteristically: Autosomal dominant, with reduced penetrance. It has also been coined the “Dominant effect of a 'recessive' mutation”.

Tumor suppressor genes are inherited in a dominant fashion.

This.

 

[Ionian]

I just noticed in FA 2013, page 82 under Incomplete penetrance: "Not all individuals witha mutant genotype show the mutant phenotype. e.g. BRCA1" (gives an example of a tumor suppressor gene mutation) helps to reaffirm my argument. Just posting in case you dont trust me

 

[ulikedaggers]

I just noticed in FA 2013, page 82 under Incomplete penetrance: "Not all individuals witha mutant genotype show the mutant phenotype. e.g. BRCA1" (gives an example of a tumor suppressor gene mutation) helps to reaffirm my argument. Just posting in case you dont trust me

Yeah, nobody should be arguing that tumor suppressors are recessive!