Divergence of mutational signatures in association with breast cancer subtype

Abstract

Abnormal molecular processes occurring throughout the genome leave distinct somatic mutational patterns termed mutational signatures. Exploring the associations between mutational signatures and clinicopathological features can unravel potential mechanisms driving tumorigenic processes.We analyzed whole genome sequencing (WGS) data of tumor and peripheral blood samples from 37 primary breast cancer (BC) patients receiving neoadjuvant chemotherapy. Comprehensive clinico-pathologic features were correlated with genomic profiles and mutational signatures. Somatic mutational landscapes were highly concordant with known BC data sets.Remarkably, we observed a divergence of dominant mutational signatures in association with BC subtype. Signature 5 was overrepresented in hormone receptor

Pan-cancer association of DNA repair deficiencies with whole-genome mutational patterns

“…Note that we excluded age-related signature 1 from the modelling, as this signature confounded by acting as a proxy for the age of the patient so that the model would be learning to differentiate old from young patients rather than patients with activity of different mutational processes or repair deficiencies. We did not exclude signature 5 although it has suggested association with age, because it also has suggested associations to the hormone receptor positive subtype of breast cancers ( Perry et al, 2022 ).…”