| First Author | Jeffers JR | Year | 2021 |
| Journal | Cancer Res | Volume | 81 |
| Issue | 9 | Pages | 2442-2456 |
| PubMed ID | 33637564 | Mgi Jnum | J:305549 |
| Mgi Id | MGI:6706770 | Doi | 10.1158/0008-5472.CAN-20-1750 |
| Citation | Jeffers JR, et al. (2021) The Common Germline TP53-R337H Mutation is Hypomorphic and Confers Incomplete Penetrance and Late Tumor Onset in a Mouse Model. Cancer Res |
| abstractText | 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. |
