Our observation of a high frequency of germline TP53 mutations in children with sporadic ADCC suggests that these children may represent probands with which to ascertain Li-Fraumeni syndrome families.
However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated.
While mutations in p53 account for a proportion of patients with LFS/LFL, future studies are needed to determine if other genes are responsible for LFS/LFL families not carrying germline p53 mutations.
The p53 gene was mapped to this chromosomal region and has been shown to be a tumor suppressor gene, and germ-line mutations of p53 recently were found to be correlated with Li-Fraumeni syndrome, a syndrome characterized by multiple neoplasms.
It appears that the group of patients with cancer who carry germline mutations of the p53 gene is more diverse than is suggested by the clinical definition of the Li-Fraumeni syndrome.
Li-Fraumeni syndrome (LFS) is a rare cancer predisposing condition caused by germline mutations in TP53, the gene encoding the TP53 transcription factor.
In light of the recent discovery of p53 point mutations in the affected Li-Fraumeni syndrome family members tested, RB overexpression may constitute a secondary event in Li-Fraumeni syndrome tumorigenesis.
These splice site alterations emphasize the need to examine both noncoding and untranslated regions of the p53 gene for germline mutations in Li-Fraumeni syndrome families.Oncogene (2000) 19, 4230 - 4235
Questionnaire data were collected for 152 women with confirmed germline TP53 variants enrolled in the National Cancer Institute's LFS study (NCT01443468); of which, 85 had breast cancer, confirmed by pathology/medical reports.
We conclude that: (i) p21WAF1-mediated senescence is the principal mode of cell death induced by < or = 15 J/m2 UV light in normal human fibroblasts; (ii) there is a threshold effect for p53-dependent apoptosis and that, in normal human cells, this threshold level is induced upon expsoure to 20 J/m2 UV; (iii) the p53 signaling pathway is malfunctional in the TP53 heterozygous LFS strains examined; and (iv) the enhanced resistance to UV-induced cell killing displayed by these LFS strains is a consequence of diminished growth arrest, which is presumably mediated by p21WAF1 and not abnormalities in an apoptotic pathway.
However, we find that even in low resource Asian settings where family history is poorly reported, germline TP53 mutations are found predominantly among breast cancer patients with a family history of LFS-linked cancers.
Li-Fraumeni-Syndrome (LFS) is an autosomal-dominant, inherited tumour predisposition syndrome associated with heterozygous germline mutations in the TP53 gene.