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

作者：Schlegelberger Brigitte^*; Kreipe Hans; Lehmann Ulrich; Steinemann Doris; Ripperger Tim; Goehring Gudrun; Thomay Kathrin; Rump Andreas; Di Donato Nataliya; Suttorp Meinolf

来源：Pediatric Blood and Cancer, 2015, 62(8): 1481-1484.

DOI：10.1002/pbc.25486

• choroid plexus carcinoma
• leukemia
• Li-Fraumeni syndrome
• sarcoma
• TP53
• uniparental disomy (UPD)

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.

• 出版日期2015-8