title: De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system.
abstract: We present a case of a 14-year-old male with a germline TP53 mutation who presented with synchronous primitive neuroectodermal tumor and choroid plexus carcinoma. Identification of synchronous brain tumors prompted genetic testing for predisposition to malignancy. Within 5 months of presentation, the child developed widely metastatic alveolar rhabdomyosarcoma. Patient DNA sequencing showed a TP53 allele with a premature stop codon in the oligomerization/nuclear export signal (NES) domain (R342ter). The child's parents, younger brother, paternal grandparents, and maternal grandmother, are without history of malignancy. The patient's brother tested negative for TP53 mutations. This case identifies a rare, de novo, germline TP53 mutation presenting with synchronous CNS malignancies and exhibiting a more fulminant course than typical cases of Li-Fraumeni syndrome.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. mschnie@emory.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schniederjan
authors.forename: Bahig
authors.initials: B
authors.lastname: Shehata
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Natia
authors.initials: N
authors.lastname: Esiashvili
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Janss
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D016545:Choroid Plexus Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D018389:Codon, Nonsense; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D017809:Fatal Outcome; D005625:Frontal Lobe / Q000473:pathology / Q000601:surgery; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009382:Neoplasms, Unknown Primary / Q000235:genetics; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000556:secondary*; D013125:Spinal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018389:Codon, Nonsense; D014750:Vincristine; D008130:Lomustine; D002945:Cisplatin