Li Fraumeni syndrome, cancer and senescence: a new hypothesis.

ABSTRACT

Li Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome characterized by germline mutations in the TP53 tumour suppressor gene. Sufferers are prone to early onset cancers, particularly sarcomas, adrenocortical carcinoma and breast cancer. Cells from LFS sufferers are known to exhibit telomere dysfunction, genomic instability and spontaneous immortalisation. It is hypothesized that these facets of the LFS host are evidence that the host environment is "primed" for carcinogenesis over and above the lack of p53 tumour suppressor function. Further, it is hypothesized that the host presents an ideal environment for "two compartment tumour metabolism" to take place. Evidence from recent studies supports this new view of LFS and suggests that disrupting certain features of the host environment may markedly reduce the incidence of cancer in LFS sufferers.