A child with Li-Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies

Pediatric Blood & Cancer
Brigitte SchlegelbergerMeinolf Suttorp

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.

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Citations

Jan 7, 2016·Frontiers in Oncology·Dawid WalerychGiannino Del Sal
Aug 19, 2015·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Gesche TallenUNKNOWN German Paediatric Brain Tumour Consortium (HIT-Network)
Nov 5, 2016·Blood·Armin ZebischHeinz Sill
Jan 18, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Rolando A R VillacisSilvia R Rogatto
May 16, 2020·Human Molecular Genetics·Jamie L MaciaszekKim E Nichols
Nov 7, 2018·Der Pathologe·T Ripperger, B Schlegelberger
Nov 1, 2016·Breast Cancer Research and Treatment·Olivia MoranJoanne Kotsopoulos
Oct 27, 2017·Journal of Medical Genetics·Mariette Renaux-PetelGaëlle Bougeard
Oct 6, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ariadne H A G OomsElizabeth J Perlman
Feb 25, 2020·Hematology/oncology Clinics of North America·Kristen E Schratz, Amy E DeZern
Jan 8, 2021·Hereditary Cancer in Clinical Practice·Ofelia CruzCinzia Lavarino

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