Inactivation of the tumor suppressor WTX in a subset of pediatric tumors. Issue 1 (5th November 2013)

• Record Type: Journal Article
• Authors: Akhavanfard, Sara; Vargas, Sara O.; Han, Moonjoo; Nitta, Mai; Chang, Clarice B.; Le, Long P.; Fazlollahi, Ladan; Nguyen, Quan; Ma, Yunqing; Cosper, Arjola; Dias‐Santagata, Dora; Han, Jae Y.; Bergethon, Kristin; Borger, Darrell R.; Ellisen, Leif W.; Pomeroy, Scott L.; Haber, Daniel A.; Iafrate, A. John; Rivera, Miguel N.
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 1(2014:Jan.)
• Page Start: 67
• Page End: 77
• Publication Date: 2013-11-05
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22118
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>WTX</italic> is a tumor suppressor gene expressed during embryonic development and inactivated in 20–30% of cases of Wilms tumor, the most common pediatric kidney cancer. <italic>WTX</italic> has been implicated in several cellular processes including Wnt signaling, <italic>WT1</italic> transcription, NRF2 degradation, and p53 function. Given that <italic>WTX</italic> is widely expressed during embryonic development and has been recently shown to regulate mesenchymal precursor cells in several organs, we tested for the potential involvement of <italic>WTX</italic> in a panel of pediatric tumors and adult sarcomas. A total of 353 tumors were screened for <italic>WTX</italic> deletions by fluorescence in situ hybridization (FISH). Discrete somatic <italic>WTX</italic> deletions were identified in two cases, one hepatoblastoma and one embryonal rhabdomyosarcoma, and confirmed by array comparative genomic hybridization. Direct sequencing of the full <italic>WTX</italic> open reading frame in 24 hepatoblastomas and 21 embryonal rhabdomyosarcomas did not identify additional mutations in these tumor types. The presence of <italic>WTX</italic> mRNA was confirmed in hepatoblastomas and embryonal rhabdomyosarcomas without <italic>WTX</italic> deletions by RNA‐in situ hybridization. Notably, tumors with evidence of <italic>WTX</italic> inactivation, Wilms tumor, hepatoblastoma and rhabdomyosarcoma, are primitive tumors that resemble undifferentiated precursor cells and are linked to overgrowth syndromes. These results indicate that <italic>WTX</italic> inactivation occurs in a wider variety of tumor types than previously appreciated and point to shared pathogenic mechanisms between a subset of pediatric malignancies. © 2013 Wiley Periodicals, Inc.</p> </abstract>