title: A Japanese patient with Li-Fraumeni syndrome who had nine primary malignancies associated with a germline mutation of the p53 tumor-suppressor gene.
abstract: We describe a patient who had nine primary malignant tumors and a germline mutation in the p53 tumor-suppressor gene, characteristically found in the Li-Fraumeni syndrome (LFS). A 15-year-old girl with no family history of cancer was referred to our hospital because of pain and swelling of the right knee. Osteosarcoma was diagnosed. The patient received chemotherapy followed by surgery and had a remission. After the age of 28 years, nine primary malignant tumors developed successively, including right breast cancer, colon cancer, malignant fibrous histiocytoma (MFH) of the abdominal wall, right lung double cancers, bilateral breast cancers, and MFH of the left thigh. This is the second highest number of types of primary malignant tumors to be reported in LFS. All tumors were treated by a multidisciplinary approach, including surgery. Genetic analysis revealed a germline missense mutation in the p53 gene (c.659 A > G), resulting in Y220C, which has been reported in three families with LFS. The patient died of lung metastasis from MFH at the age of 37 years. Despite the multiple tumors, repeated induction of remissions resulted in long survival. Our findings suggest that a multidisciplinary approach to treatment, including surgery, is beneficial in patients with LFS.
authors.affiliation: Department of Orthopedic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, 135-8550, Japan. nizawa-tky@umin.ac.jp
authors.forename: Naohiro
authors.initials: N
authors.lastname: Izawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Jun
authors.initials: J
authors.lastname: Manabe
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tanizawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Hoshi
authors.forename: Toshio
authors.initials: T
authors.lastname: Shigemitsu
authors.forename: Rikuo
authors.initials: R
authors.lastname: Machinami
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kanda
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.forename: Masami
authors.initials: M
authors.lastname: Arai
authors.forename: Shuya
authors.initials: S
authors.lastname: Shirahama
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kawaguchi
mesh_terms: D000293:Adolescent; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D020125:Mutation, Missense; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010375:Pedigree