Unexpected COSMIC Signatures in Breast Cancer Samples (SBS10d and SBS22b)

[hilmklnc]

Hello,

I am working with 560 breast cancer samples from a previous study ((Nik-Zanial, 2016)) and ran SigProfilerExtractor using COSMIC v3.4. I noticed that the suggested results included signatures like SBS10d and SBS22b, which I would not expect to be associated with breast tissue.

In the De_Novo_MutationType_Probabilities file within the suggested solution, I observed that both SBS22b and SBS96 have zero probabilities across all samples. Additionally, in the activity files, these signatures also show zero activity scores for all samples. I am curious why these COSMIC signatures were still identified in the de novo results despite showing no activity in the output. Could you clarify why they appear in the results even with zero activity?

Furthermore, I noticed high probability values linked to SBS10d in some samples. When I individually examined the mutations associated with SBS10d, I could not find that these mutations fall into the POLD1, which is typically linked to this signature. Could you explain why SBS10d would still have high probabilities without POLD1-associated mutations?

Thank you for your insights and support!
Hilmi