title: A child with Li-Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies.
abstract: Here we report on a child with Li-Fraumeni syndrome with a de novo TP53 mutation c.818G>A, who developed three malignancies at the age of 4 months, 4 and 5 years, respectively. We show that (i) in the choroid plexus carcinoma, the germline mutation was detected in a homozygous state due to copy-neutral LOH/uniparental disomy, (ii) in the secondary AML, a complex karyotype led to loss of the wild-type TP53 allele, (iii) in the Wilms tumor, the somatic mutation c.814G>A led to compound heterozygosity. The findings show that the complete inactivation of TP53 by different mechanisms is an important step towards tumorigenesis.
authors: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors: Brigitte
authors: B
authors: Schlegelberger
authors: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors: Hans
authors: H
authors: Kreipe
authors: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors: Ulrich
authors: U
authors: Lehmann
authors: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors: Doris
authors: D
authors: Steinemann
authors: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors: Tim
authors: T
authors: Ripperger
authors: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors: Gudrun
authors: G
authors: Göhring
authors: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors: Kathrin
authors: K
authors: Thomay
authors: Institute for Clinical Genetics, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
authors: Andreas
authors: A
authors: Rump
authors: Institute for Clinical Genetics, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
authors: Nataliya
authors: N
authors: Di Donato
authors: Department of Pediatric Hematology and Oncology, University Hospital Dresden, Germany.
authors: Meinolf
authors: M
authors: Suttorp
mesh_terms: D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D016545:Choroid Plexus Neoplasms / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Li-Fraumeni syndrome; TP53; choroid plexus carcinoma; leukemia; sarcoma; uniparental disomy (UPD)