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At a glance

Genetically transmitted Cancer Predisposition Syndrome associated with soft tissue sarcoma, breast cancer, leukemia osteosarcoma, melanoma, and cancer of the colon, pancreas, adrenal cortex, and brain.


Sarcoma, Breast Syndrome, Leukemia, and Adrenal Gland (SBLA) Syndrome; Sarcoma Family Syndrome.


Li-Fraumeni Syndrome was first described in 1969 by two American physicians working at the National Institute of Cancer, Frederick Pei Li (1940-2015) and Joseph F. Fraumeni Jr. (1933) who observed this syndrome after reviewing medical records and death certificates of 648 children affected with rhabdomyosarcoma.


It is defined by the association of a proband with a sarcoma who is diagnosed before the proband, ie, the affected person who ascertains independently of his relatives in a genetic study, is age 45 years, a first-degree relative with any cancer who is younger than 45 years, and a first-or second-degree relative with any cancer who is younger than 45 years or who has a sarcoma at any age.


The exact incidence remains unknown. Fewer than 400 families have been reported worldwide. It is reported that 300,000 Brazilian are carriers of the R337H variant that is known to predispose to multiple cancer development and LFS.

Genetic inheritance

Autosomal dominant. The discovery in 1990 of inherited mutations of the tumor suppressor gene P53 was established in most affected families. More than 50% of LFS patients have an identifiable disease-causing mutation in the TP53 gene (gene map locus is 17p13.1), 95% of which can be detected by direct sequence-based deoxyribonucleic acid (DNA) testing (clinically available). The CHEK2 gene is also known to be associated in a few families with LFS, but CHEK2 testing is only available on a research basis.


The TP53 gene encodes a cellular tumor antigen protein (the “guardian of the genome”) that complexes to the large T antigen of SV40. This protein determines whether cells undergo arrest for purposes of DNA repair or programmed cell death (apoptosis). In case of damaged DNA, the normal cellular tumor antigen p53 protein either (1) transcriptionally activates downstream genes to repair the DNA or (2) directly signals a “sensor” molecule that proceeds with apoptosis. Mutant cellular tumor antigen p53 is able to cooperate with RAS oncogene products and blocks normal cellular tumor antigen p53 protein from appropriately binding, thus favoring the development or maturation of many tumor types.


Molecular genetics (direct sequence-based DNA testing).

Clinical aspects

LFS is a highly penetrant Cancer Syndrome. Original descriptions of LFS consisted of autosomal dominant patterns of osteosarcomas, soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenal cortical tumors, and acute leukemias. Since ...

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