Hi!
I have a very basic question about cancer. What does it mean from a cancer biology perspective, to have a mutation at the RNA level and not the DNA level? If I have both types of data and I found a mutation just in the RNA seq data and not in the DNA data, what does that imply?
Thanks a lot!
This is not a bioinformatics question, but there will likely be some interest in discussing it.
Most likely the mutation means nothing in terms of cancer.
Assuming that it is real and not an artifact of sequencing, a mutation in the coding region can be synonymous, and therefore silent. It can also be a part of RNA editing (C->U or A->I), which is typically regulated and therefore normal. Finally, the mutation may be introduced during sequencing, which is rare but still possible. All of the examples above either would not lead to mutations at a protein level, or those would be desired mutations as part of RNA editing.
I guess it is possible that RNA polymerase would make a mutation in enough molecules for it to be captured by sequencing, but that seems unlikely.
A mutation in coding DNA (and subsequently captured by RNA-seq) could lead to protein mutation with a good probability. Mutations in the third codon position are silent for 7 out of 20 amino-acids, and sometimes even mutation at the first codon position are silent. Still, that leaves plenty of combinations where a mutation in coding DNA would change protein sequence, so I wouldn't call it unlikely.
Thanks a lot again! I think that it is possible to have mutation in coding DNA that are not capture by RNA-seq. For example, if you have a mutation at the exon end (coding DNA, e.g. last three nucleotide of the exon), it could affect the splicing process and if the exon is skipped, you shouldn't be able to capture that mutation in RNAseq. Right?
RNA expression is tissue specific. Are you looking comparing RNA and DNA data from the same tissue sequenced around the same time?
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What is the level of support do you have for that observation in terms of coverage?
Hi GenoMax, thanks for your question! it is low, I have in total 20 reads and the mutation is just in 2 of them.
That would support a sequencing error as a likely cause of mutation, although it is possible that there is a small fraction of mutations in the pool that are caused by RNA polymerase.