{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:42:05Z","timestamp":1774698125206,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T00:00:00Z","timestamp":1383609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:p><jats:italic>WTX<\/jats:italic> is a tumor suppressor gene expressed during embryonic development and inactivated in 20\u201330% of cases of Wilms tumor, the most common pediatric kidney cancer. <jats:italic>WTX<\/jats:italic> has been implicated in several cellular processes including Wnt signaling, <jats:italic>WT1<\/jats:italic> transcription, NRF2 degradation, and p53 function. Given that <jats:italic>WTX<\/jats: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 <jats:italic>WTX<\/jats:italic> in a panel of pediatric tumors and adult sarcomas. A total of 353 tumors were screened for <jats:italic>WTX<\/jats:italic> deletions by fluorescence in situ hybridization (FISH). Discrete somatic <jats:italic>WTX<\/jats: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 <jats:italic>WTX<\/jats:italic> open reading frame in 24 hepatoblastomas and 21 embryonal rhabdomyosarcomas did not identify additional mutations in these tumor types. The presence of <jats:italic>WTX<\/jats:italic> mRNA was confirmed in hepatoblastomas and embryonal rhabdomyosarcomas without <jats:italic>WTX<\/jats:italic> deletions by RNA\u2010in situ hybridization. Notably, tumors with evidence of <jats:italic>WTX<\/jats: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 <jats:italic>WTX<\/jats: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. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22118","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T09:48:33Z","timestamp":1383644913000},"page":"67-77","source":"Crossref","is-referenced-by-count":6,"title":["Inactivation of the tumor suppressor <i>WTX<\/i> in a subset of pediatric tumors"],"prefix":"10.1002","volume":"53","author":[{"given":"Sara","family":"Akhavanfard","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"},{"name":"Cancer Center, Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara O.","family":"Vargas","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston MA"},{"name":"Department of Pathology Children's Hospital Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moonjoo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Nitta","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarice B.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long P.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ladan","family":"Fazlollahi","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Affymetrix Santa Clara CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqing","family":"Ma","sequence":"additional","affiliation":[{"name":"Affymetrix Santa Clara CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjola","family":"Cosper","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora","family":"Dias\u2010Santagata","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Y.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Bergethon","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrell R.","family":"Borger","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif W.","family":"Ellisen","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott L.","family":"Pomeroy","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston MA"},{"name":"Department of Neurology  Children's Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Haber","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital  Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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