SNP Shot: Genomic Insights

Li-Fraumeni syndrome (LFS) is a rare genetic condition that significantly elevates the risk of developing various cancers, especially in children and young adults.

Cancers frequently linked to LFS include breast cancer, osteosarcoma (a type of bone cancer), and soft tissue sarcomas (cancers of soft tissues like muscle). Furthermore, individuals with LFS are more susceptible to brain tumors, leukemias (cancers of blood-forming tissues), and adrenocortical carcinoma, a cancer affecting the outer layer of the adrenal glands. Other cancers also occur with greater frequency in individuals with this syndrome.

Li-Fraumeni-like syndrome (LFL) is a related condition that shares many characteristics with classic LFS. Both syndromes increase the likelihood of developing multiple cancers, often starting in childhood. However, the specific types of cancers observed within affected families can differ between LFS and LFL.

Inheritance:

LFS follows an autosomal dominant inheritance pattern. This means that having just one copy of the mutated gene in each cell is enough to increase cancer risk. In most cases, individuals with LFS inherit the altered gene from a parent who also has the condition. However, in 7 to 20 percent of cases, the altered gene arises from a new (de novo) mutation. This new mutation occurs during the formation of egg or sperm cells, or very early in the individual's development. For a cancer to develop in individuals with LFS, a second mutation must occur in the other copy of the TP53 gene within the body's cells during their lifetime. Cells with two mutated copies of this gene are unable to produce functional TP53 protein, which normally prevents tumor formation. Because nearly everyone who inherits one TP53 gene mutation will eventually acquire a second mutation in some cells, tumors commonly develop in tissues such as breast, bone, or muscle, leading to the cancers characteristic of LFS.