Publications by authors named "Madeline Dennis"
APOBEC-induced mutations occur in 50% of sequenced human tumors, with APOBEC3A (A3A) being a major contributor to mutagenesis in breast cancer cells. The mechanisms that cause A3A activation and mutagenesis in breast cancers are still unknown. Here, we describe factors that influence basal A3A mRNA transcript levels in breast cancer cells.
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- APOBEC cytidine deaminases, specifically APOBEC3A, contribute to genetic instability in cancer, particularly through the creation of mutations in breast cancer.
- The study reveals that using proteasome inhibitors boosts the levels of A3A mRNA significantly, by approximately 100 times, suggesting that this treatment activates the transcription of A3A rather than just preventing its breakdown.
- Increased A3A levels lead to greater cytidine deaminase activity, reduced cell growth, and more DNA damage, indicating that proteasome dysfunction may enhance genetic diversity in tumors and affect how patients respond to treatments.
The initiation, progression, and relapse of cancers often result from mutations occurring within somatic cells. Consequently, processes that elevate mutation rates accelerate carcinogenesis and hinder the development of long-lasting therapeutics. Recent sequencing of human cancer genomes has identified patterns of mutations, termed mutation signatures, many of which correspond to specific environmentally induced and endogenous mutation processes.
View Article and Find Full Text PDFAPOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast cancer (BRCA). We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A expression is responsible for cytidine deamination in multiple BRCA cell lines.
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