Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen:
Volltext verfügbar? / Dokumentlieferung
doi:10.22028/D291-41031
Titel: | TRIM28 haploinsufficiency predisposes to Wilms tumor |
VerfasserIn: | Diets, Illja J. Hoyer, Juliane Ekici, Arif B. Popp, Bernt Hoogerbrugge, Nicoline van Reijmersdal, Simon V. Bhaskaran, Rajith Hadjihannas, Michel Vasileiou, Georgia Thiel, Christian T. Seven, Didem Uebe, Steffen Ilencikova, Denisa Waanders, Esmé Mavinkurve-Groothuis, Annelies M. C. Roeleveld, Nel de Krijger, Ronald R. Wegert, Jenny Graf, Norbert Vokuhl, Christian Agaimy, Abbas Gessler, Manfred Reis, André Kuiper, Roland P. Jongmans, Marjolijn C. J. Metzler, Markus |
Sprache: | Englisch |
Titel: | International Journal of Cancer |
Bandnummer: | 145 |
Heft: | 4 |
Seiten: | 941-951 |
Verlag/Plattform: | Wiley |
Erscheinungsjahr: | 2019 |
Freie Schlagwörter: | Wilms tumor haploinsufficiency TRIM28 genetic predisposition |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Two percent of patients with Wilms tumors have a positive family history. In many of these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families with two affected individuals with Wilms tumors, we identified truncating mutations in TRIM28. Subsequent mutational screening of germline and tumor DNA of 269 children affected by Wilms tumor was performed, and revealed seven additional individuals with germline truncating mutations, and one individual with a somatic truncating mutation in TRIM28. TRIM28 encodes a complex scaffold protein involved in many different processes, including gene silencing, DNA repair and maintenance of genomic integrity. Expression studies on mRNA and protein level showed reduction of TRIM28, confirming a loss-of-function effect of the mutations identified. The tumors showed an epithelial-type histology that stained negative for TRIM28 by immunohistochemistry. The tumors were bilateral in six patients, and 10/11 tumors are accompanied by perilobar nephrogenic rests. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Additionally, the tumors showed very few mutations in known Wilms tumor driver genes, suggesting that loss of TRIM28 is the main driver of tumorigenesis. In conclusion, we identified heterozygous germline truncating mutations in TRIM28 in 11 children with mainly epithelial-type Wilms tumors, which become homozygous in tumor tissue. These data establish TRIM28 as a novel Wilms tumor predisposition gene, acting as a tumor suppressor gene by LOH. |
DOI der Erstveröffentlichung: | 10.1002/ijc.32167 |
URL der Erstveröffentlichung: | https://doi.org/10.1002/ijc.32167 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-410310 hdl:20.500.11880/36822 http://dx.doi.org/10.22028/D291-41031 |
ISSN: | 1097-0215 0020-7136 |
Datum des Eintrags: | 10-Nov-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fijc.32167&file=ijc32167-sup-0001-supinfo.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fijc.32167&file=ijc32167-sup-0002-Tables.xlsx |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Pädiatrie |
Professur: | M - Prof. Dr. Norbert Graf |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Es gibt keine Dateien zu dieser Ressource.
Alle Ressourcen in diesem Repository sind urheberrechtlich geschützt.