Li-Fraumeni Syndrome

These findings suggest that, despite its rare occurrence, Peutz-Jeghers syndrome is associated with a markedly increased risk of breast cancer. The gene mutated in Peutz-Jeghers syndrome was recently identified on chromosome 19 and is now known to be STKII/LKB1, a putative tumor-suppressor gene that encodes a protein kinase. The association between mutations in STKII/LKB1 and Peutz-Jeghers syndrome was subsequently confirmed in 20 additional families. 

Muir-Torre Syndrome
Muir-Torre syndrome, a variant of hereditary nonpolyposis colon cancer (HNPCC, also called Lynch Type II syndrome) is the eponym given to the association between multiple skin tumors and multiple benign and malignant tumors of the upper and lower gastrointestinal and genitourinary tracts. Many of the manifestations of Muir-Torre syndrome are common lesions (basal cell carcinomas, keratoacanthomas, and colonic diverticula) in distributions similar to that in the general population but with earlier age of onset in affected individuals.

Females with the syndrome reportedly have an increased tendency to breast cancer, particularly after menopause, although lifetime risk has not been calculated. Multiple genes responsible for HNPCC have been described, including MLH1 and MSH2.

Mutations in these genes are thought to lead to development of HNPCC through accumulation of DNA replication errors and associated subsequent genome instability. Confirmation that Muir-Torre syndrome is a variant of HNPCC occurred with the identification of germ-line mutations in MHS2 in individuals with the syndrome. A truncating mutation in MLH1 also has been detected in a Muir-Torre syndrome family.


Angela DeMichele and Barbara L. Weber

A. DeMichele: Departments of Medicine and Epidemiology, The University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania
B. L. Weber: Departments of Medicine and Genetics, Breast Cancer Program, Population Science and Cancer Control, The University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania


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