Germline mutations of p53

In 1969, Li and Fraumeni identified families in
whom other members were affected with
diverse types of tumors, mainly soft-tissue sarcomas,
early-onset breast cancer, brain cancers,
cancer of the bone (osteosarcoma) and bone
marrow(leukemias), and carcinoma of the lung,
pancreas, and adrenal cortex. Similar observations
had been reported as “cancer family syndrome”
by Lynch. This autosomal dominant
cancer syndrome is called the Li–Fraumeni
syndrome (McKusick 114480). In the pedigree
shown in panel 1, four individuals (II-2, II-3, III-
1, III-2) are affected by different types of
tumors. A mutation in codon 248 of the p53
gene (CGG arginine, to TGG, tryptophan) is
present in these patients. The mutation is also
present in individuals I-1 and III-5. This places
these individuals at increased risk for one of the
types of cancer mentioned above and shown in
panel 2. In contrast, absence of the mutation in
individuals III-3 and III-4 indicates that they do
not have an increased risk of cancer (Data of
D. Malkin). A subset of patients with Li–Fraumeni
syndrome does not show p53 mutations.