In order to determine the frequency and distribution of germ-line p53 mutations in LFS, we sequenced the 10 coding exons of the p53 gene in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome.
These findings identify an important subgroup of young patients with cancer who carry germline mutations in the p53 tumor-suppressor gene but whose family histories are not indicative of the Li-Fraumeni syndrome.
Most of the genes listed are responsible for various well-defined cancer syndromes, such as CDKN2A (familial atypical mole-multiple melanoma, FAMMM), the mismatch repair genes (Lynch Syndrome), TP53 (Li-Fraumeni syndrome), APC (familial adenomatous polyposis), and BRCA2 (breast-ovarian familial cancer), where PC is part of the cancer spectrum of the disease.
It is believed that the loss of p53 wild type function contributes to immortalization of these LFS fibroblasts, but it is not clear if this is sufficient.
These results suggest germline p53 mutations to possibly be responsible for a subset of young adult patient with multiple malignant tumors, even those not meeting the clinical criteria for LFS or LFL.
TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.
A significant prevalence of homozygous MDM2 SNP309 G in the LFS Suggestive group (p < 0.0005) confirms its contribute to cancer susceptibility, also highlighted in LFSTP53 positive families.
p53 mutations isolated in yeast based on loss of transcription factor activity: similarities and differences from p53 mutations detected in human tumors.
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.