TY  - JOUR
AU  - Weijers, Dilys D
AU  - Hirsch, Steffen
AU  - Bakhuizen, Jette J
AU  - van Engelen, Nienke
AU  - Kester, Lennart A
AU  - Kranendonk, Mariëtte E G
AU  - Hiemcke-Jiwa, Laura S
AU  - de Vos-Kerkhof, Evelien
AU  - Loeffen, Jan L C
AU  - Autry, Robert
AU  - Pajtler, Kristian
AU  - Jäger, Natalie
AU  - Jongmans, Marjolijn C J
AU  - Kuiper, Roland P
TI  - Molecular analysis of cancer genomes in children with Lynch syndrome: Exploring causal associations.
JO  - International journal of cancer
VL  - 154
IS  - 8
SN  - 0020-7136
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2024-00034
SP  - 1455-1463
PY  - 2024
N1  - 2024 Apr 15;154(8):1455-1463
AB  - Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants in a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting a causal relationship. For LS-spectrum (LSS) cancers, including high-grade gliomas and colorectal cancer, causality has been supported by typical MMR-related tumor characteristics, but for non-LSS cancers, causality is unclear. We characterized 20 malignant tumors of 18 children with LS, including 16 non-LSS tumors. We investigated second hits, tumor mutational load, mutational signatures and MMR protein expression. In all LSS tumors and three non-LSS tumors, we detected MMR deficiency caused by second hit somatic alterations. Furthermore, these MMR-deficient tumors carried driver variants that likely originated as a consequence of MMR deficiency. However, in 13 non-LSS tumors (81
KW  - Lynch syndrome (Other)
KW  - cancer predisposition (Other)
KW  - mismatch repair (Other)
KW  - mutational signatures (Other)
KW  - pediatric cancer (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38175816
DO  - DOI:10.1002/ijc.34832
UR  - https://inrepo02.dkfz.de/record/286670
ER  -