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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.

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

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Li-Fraumeni syndrome is defined by the association of a proband with a sarcoma who is diagnosed before the proband, i.e., 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.

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Fewer than 400 families reported worldwide.

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Autosomal dominant. 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 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.

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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.

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Molecular genetics (direct sequence-based DNA testing).

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Li-Fraumeni syndrome 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 then, reports of LFS families suggest excess rates of melanoma; cancer of the stomach, colon, pancreas, and esophagus; and gonadal germ cell tumors diagnosed at early ages. At-risk children should undergo examination on an annual basis: complete physical examination, blood cell count, urinalysis, abdominal ultrasonography examination, and organ-targeted surveillance based on family history.

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No specific precautions to be taken before anesthesia. However, a thorough evaluation of possible complications associated with the type of malignancy diagnosed must be done. Proper laboratory investigations for coagulation disorders, anemia, and electrolyte imbalances must be performed prior to surgery and anesthesia.

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Anesthetic considerations are those indicated by the pathology involved.

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No specific pharmacological implications other than those associated with the pathology involved and the treatment performed preoperatively.

Birch JM, Alston RD, McNally RJ, et al: Relative frequency and morphology of cancers in carriers of germline TP53 mutations. ...

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