NextStep FL5 B/B #18

[sapientnarwhal]

So this question seemed incorrect. The control cell line is BT134

The CRC200 cell line should have 1 non-functional copy of p53 and 1 functional copy.
I reasoned that due to p53 haploinsufficiency (p53 is a TS oncogene, typically LOF result in cancer phenotype), the untreated CRC200 cell lines would exhibit uncontrolled proliferation ~700 colonies.

Once CRC200 is transfected with WT p53 plasmid, we would expect to observe rescue of WT p53 function (now has 2 functional WT copties of p53) through growth arrest and cell counts similar to the BT134 control ~15 colonies.

The NS explanation noted that the p53 is overactive which makes little sense as we are only provided with the info that it results from a nonfunctional p53 copy (premature termination of translation). For the sake of MCAT simplicity, I always thought that we should assume proto-oncogenes to be overactive, as GOF in proto-oncogenes accelerates growth and proliferation.

@NextStepTutor_1

---

Members don't see this ad.

 

[NextStepTutor_1]

Hi @sapientnarwhal -

Thanks for the excellent question. p53 haploinsufficiency seems like the crux of the issue here. The reasoning of this question is that when a single LOF mutation occurs, heterozygous cells should be be able to compensate and have their function remain intact. Therefore, adding either a wild-type or a mutant plasmid to such a cell should not make much of a difference.

This general assumption about heterozygotes being able to compensate for loss-of-function mutations is a rule of thumb, albeit one that is commonly used. As always, the real world is more complicated, and some research has suggested that p53 may show haploinsufficiency, meaning that this assumption might not apply. I'll bring this issue to our FL development team to discuss. In general, the MCAT doesn't necessarily reflect the cutting edge of research, and there is a lot of MCAT-level science that gets more complicated if you dig deeper, but it can be a fine line to walk.

Also, to clarify, the point about an "overactive protein product" in the explanation does not apply to p53, it applies to oncogenic gain-of-function mutations in contrast to the loss of function mutation in p53. Hope this helps clarify the question!