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A child with Li–Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies
Author(s) -
Schlegelberger Brigitte,
Kreipe Hans,
Lehmann Ulrich,
Steinemann Doris,
Ripperger Tim,
Göhring Gudrun,
Thomay Kathrin,
Rump Andreas,
Di Donato Nataliya,
Suttorp Meinolf
Publication year - 2015
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25486
Subject(s) - loss of heterozygosity , li–fraumeni syndrome , germline mutation , uniparental disomy , allele , germline , genetics , medicine , cancer research , carcinogenesis , mutation , somatic cell , wilms' tumor , karyotype , biology , cancer , chromosome , gene
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. Pediatr Blood Cancer 2015;62:1481–1484. © 2015 Wiley Periodicals, Inc.