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4.4 years ago
CY
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750
It is almost common sense that local amplification of gene increase the its mRNA expression. I recently heard that large scale SCNA (such as arm-level amplification) does not increase the mRNA expression level of gene within the region. I did some analysis (SCNA is determined by SNP array and NGS, mRNA expression is measured by RNA-Seq) and found that this is indeed the case. it seems like a common acknowledgement (For example, MET amplification is the sign of anti-EGFR drugs only when the amplification is local). Is there any technical bias or biological explanation that I am missing here? Or is it something that has not have a answer yet ?
The only thing that comes to my mind is that far from all the genes are dosage sensitive. I'd repeat this analysis, using only dosage-sensitive genes, and if it will change nothing - then I'd start to think about more complex explanations.
We have already tested this on a number of gene. It looks like not a gene specific phenomenon. All genes we have tested shown increased expression level in times of local amplification. But in times of arm-level amplification, the expression did not change at all. BTW, this seems to be well accepted role in companion diagnostic. For example, MET amplification is the sign of anti-EGFR drugs only when the amplification is local.
Do you see the same picture with arm-level deletions?
Not yet. Will try that very soon.
Deletion of both local and arm level result in same degree of expression reduction. In another word, deletion does not share the phenomenon we are talking about.
great news. could you share the papers you mentioned before (that it was shown previously that aneuploidies do not affect the expression)? I can also google myself, but I'd like to share the same knowledge so we will be able to discuss the thoughts in more details... Like, here is the whole paper proving different thing: https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/febs.13591%4010.1111/%28ISSN%291742-4658.111 , another one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737485/ (special attention to figure 2 - the change in expression is quite subtle), I would like to know both sides.