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Updated: May 23, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers
Nabamita Boruah1, David Hoyos2, Renyta Moses1
1Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer (BC) is the most common cancer in LFS females. Here, we perform a multimodal analysis, comparing LFS-BC with sporadic premenopausal breast cancer which shows that nearly all LFS-BC undergo biallelic loss of TP53, with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibit a high burden of short amplified aneuploid segments. Pro-apoptotic p53 target genes BAX and TP53I3 fail to be up-regulated in LFS-BC unlike in sporadic BC compared to normal breast tissue. LFS-BC has lower CD8 + T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC is marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue.
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