Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers - PubMed
4 hours ago
- #TP53
- #Tumor Evolution
- #Li-Fraumeni Syndrome
- Germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), with breast cancer as the most common cancer in LFS females.
- LFS breast cancers (LFS-BC) typically undergo biallelic loss of TP53 and show no recurrent oncogenic variants except ERBB2 amplification.
- Compared to sporadic premenopausal breast cancer, LFS-BC exhibits a high burden of short amplified aneuploid segments.
- Pro-apoptotic p53 target genes BAX and TP53I3 fail to up-regulate in LFS-BC, unlike in sporadic breast cancer.
- LFS-BC has lower CD8+ T-cell infiltration but higher levels of proliferating cytotoxic T-cells compared to sporadic breast cancer.
- Progression from in situ to invasive LFS-BC is marked by increased chromosomal instability and decreased proliferating cytotoxic T-cells.