Klin Padiatr 2019; 231(03): 159
DOI: 10.1055/s-0039-1687131
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

TRIM28 haploinsufficiency predisposes to Wilms tumor

M Metzler
1   University Hospital Erlangen, Department of Pediatrics, Erlangen, Germany
,
IJ Diets
2   Radboud University Medical Center, Department of Human Genetics, Nijmegen, The Netherlends
,
J Hoyer
3   Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Pediatrics, Erlangen, Germany
,
J Wegert
4   University of Würzburg, Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, Würzburg, Germany
,
N Graf
5   Saarland University, Department of Pediatric Hematology and Oncology, Medical Center Homburg/Saar, Homburg, Germany
,
C Vokuhl
6   Christian Albrechts University, Kiel Pediatric Tumor Registry, Section of Pediatric Pathology, Department of Pathology, Kiel, Germany
,
M Gessler
4   University of Würzburg, Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, Würzburg, Germany
,
RP Kuiper
7   Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
,
MCJ Jongmans
8   University Medical Center Utrecht, Department of Genetics, Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Publication Date:
20 May 2019 (online)

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Background:

Most Wilms tumor diagnoses occur in sporadic patients. About 2% of cases have one or more relatives affected by Wilms tumor. The currently known repertoire of oncogenic driver mutations includes WT1, CTNNB1, AMER1, MYCN, SIX1/2 and several miRNA processing genes. The underlying genetic cause of some familial cases remains unexplained, indicating the existence of other Wilms tumor predisposition genes.

Method:

Two families with two affected individuals were analyzed using germline exome sequencing. Additional 269 children affected with Wilms tumor were screened for mutations in this gene by targeted enrichment sequencing.

Results:

We identified heterozygous germline truncated mutations in TRIM28 in eleven children that become homozygous in the Wilms tumor tissue. The tumors showed an epithelial-type histology that stained negative for TRIM28 by immunohistochemistry. MRNA and protein level of TRIM28 were reduced suggesting that loss of TRIM28 is the main driver of tumorigenesis.

Conclusions:

Our data identify TRIM28 as a novel Wilms tumor predisposition gene, functioning as a classical tumor suppressor gene in Wilms tumor.