| Autor: |
John R, Jeffers, Emilia M, Pinto, Jerold E, Rehg, Michael R, Clay, Jinling, Wang, Geoffrey, Neale, Richard J, Heath, Guillermina, Lozano, Enzo, Lalli, Bonald C, Figueiredo, Alberto S, Pappo, Carlos, Rodriguez-Galindo, Wenan, Chen, Stanley, Pounds, Raul C, Ribeiro, Gerard P, Zambetti |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Cancer Res |
| ISSN: |
1538-7445 |
| Popis: |
The TP53-R337H founder mutation exists at a high frequency throughout southern Brazil and represents one of the most common germline TP53 mutations reported to date. It was identified in pediatric adrenocortical tumors in families with a low incidence of cancer. The R337H mutation has since been found in association with early-onset breast cancers and Li-Fraumeni syndrome (LFS). To study this variability in tumor susceptibility, we generated a knockin mutant p53 mouse model (R334H). Endogenous murine p53-R334H protein was naturally expressed at high levels in multiple tissues and was functionally compromised in a tissue- and stress-specific manner. Mutant p53-R334H mice developed tumors with long latency and incomplete penetrance, consistent with many human carriers being at a low but elevated risk for cancer. These findings suggest the involvement of additional cooperating genetic alterations when TP53-R337H occurs in the context of LFS, which has important implications for genetic counseling and long-term clinical follow-up. SIGNIFICANCE: A p53-R334H knockin mouse serves as an important model for studying the most common inherited germline TP53 mutation (R337H) that is associated with variable tumor susceptibility. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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