Li-Fraumeni syndrome (LFS) is a rare inherited cancer susceptibility disorder. More directly stated the syndrome is caused by a mutation in a tumor suppressor gene, p53, that predisposes those affected to multiple malignancies. A recent article in the Journal of Clinical Oncology attempted to correlate specific mutation types with clinical presentation. The syndrome is not uniform and has a great deal of variability depending on the specific genetic alteration in p53 gene. As already know a striking 43% of the 322 patients evaluated had developed multiple malignancies. Research should focus on developing treatment protocols that are less genotoxic to reduce the risk of secondary tumors in patients with LFS. The types of tumors also varies based on age of presentation.
Children with LFS present with:
Osteosarcomas 30%
Adrenocortical carcinomas 27%
CNS tumors 26%
Soft tissue sarcomas 23%
Adults with LFS present with:
Breast carcinomas in 79% women
Soft tissue sarcomas 27%
The severity of the disease also varies based on the type of germline mutation in p53 tumor suppressor gene
Dominant-negative missense mutations:
More severe mutation
Earlier tumor onset
Seen more in the childhood LFS presentation
Loss of function or inactivating mutations (nonsense mutations, frameshift mutations, or genetic rearrangements):
Less severe alterations
Later tumor onset
Primarily seen in cancers occurring in adults
Nondominant-negative missense mutations:
Intermediate class based on clinical severity
More details on the cancer implications of p53 mutations and clinical stratification based on varied mutations can be found in the attached manuscript:
