Question about p53 annotations in METABRIC

Question

[Avro]

Hi everyone,

I am working with a breast cancer dataset called METABRIC. It contains p53 sequencing information like so:

MB-AD-0002+ex5,6+chr17**:**7519122+12521A>AC+178H>H/P+MISSENSE+FR+FR

I would greatly appreciate the community's feedback. I want to understand, so that I can cross-reference these mutations with databases.

This is what I think I understand: there is a cytosine that is inserted after an Adenosine which causes a frame-shift. This frame-shift causes the 178th amino acid (Histidine) to be converted into a Proline. If so, I assume that the remaining codons will be different. I am also confused about what ex5,6+7519122 +12521 mean.

Thank you very much for your time.

Answer 1

[Devon Ryan]

chr17:7519122 should be the genomic coordinate. That base should then be the 12521st of at least one of the transcripts of the gene that's being changed (or maybe they take some sort of union gene model for this, who knows). Presumably the change directly affects exons 5 and 6 (perhaps depending on the transcript, since the change appears to be in exon 5 of most of them...unless maybe there's a stop codon created in exon 6). Anyway, if you want a definitive answer then you might have to ask the METABRIC people.

[Avro]

Thank you! I did contact them and waiting their answer.