Germline Mutations of the p53 Tumor-Suppressor Gene in Children and Young Adults with Second Malignant Neoplasms

THE p53 tumor-suppressor gene, located on the short arm of human chromosome 17, 1 , 2 encodes a 53-kd nuclear phosphoprotein involved in the control of cellular proliferation. 3 4 5 6 7 Acquired mutations in p53 are the most common tumor-specific genetic changes observed to date, having been identified in most major cancer types. 8 , 9 In addition, germline mutations in p53 were recently identified in families with the Li—Fraumeni syndrome, a rare familial cancer syndrome characterized by an unusually high incidence of sarcomas, premenopausal breast cancers, and other diverse neoplasms, particularly brain tumors, leukemias, and adrenocortical carcinomas. 10 11 12 13 14 15 Families with Li—Fraumeni syndrome have been described as including a proband . . .