{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:17:58Z","timestamp":1790702278472,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T00:00:00Z","timestamp":1476230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["5T32GM007454"],"award-info":[{"award-number":["5T32GM007454"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Atypical teratoid rhabdoid tumors of the central nervous system are rare, highly malignant, embryonal tumors most often occurring in children under age 3 years. Most are due to a somatic change in tumor suppressor gene <jats:italic>SMARCB1<\/jats:italic> followed by a second\u2010hit, typically loss of heterozygosity, best detected on immunohistochemical staining. Despite the noteworthy genetic homogeneity of atypical teratoid rhabdoid tumors, relatively little is known about the oncogenic mechanisms that lead to biallelic inactivation of <jats:italic>SMARCB1<\/jats:italic>. Herein, we describe a patient with constitutional ring chromosome 22, Phelan\u2013McDermid syndrome and atypical teratoid rhabdoid tumor of the brain. During mitosis, sister chromatids of a ring chromosome may form interlocking and dicentric rings, resulting in chromosomal loss, complex karyotypes, and ongoing somatic variation. We hypothesized that the inherent instability of the patient's ring chromosome could lead to mosaic monosomy chromosome 22, resulting in allelic inactivation of the tumor\u2010suppressor gene <jats:italic>SMARCB1<\/jats:italic> and AT\/RT if a second\u2010hit occurred. Utilizing high\u2010density microarray technology to analyze peripheral blood and tumor tissue, we confirmed this oncogenic mechanism, previously undescribed in patients with atypical teratoid rhabdoid tumors. Our data demonstrate chromosomal loss as a consequence of ring chromosome instability serving as the first hit in oncogenesis. This rare but possibly under\u2010recognized mechanism is important to note in children with ATRT and syndromic features. Further investigation is warranted to assess if this oncogenic mechanism has management and\/or prognostic implications. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37993","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T22:45:41Z","timestamp":1476398741000},"page":"245-249","source":"Crossref","is-referenced-by-count":15,"title":["Description of a new oncogenic mechanism for atypical teratoid rhabdoid tumors in patients with ring chromosome 22"],"prefix":"10.1002","volume":"173","author":[{"given":"Heather M.","family":"Byers","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Department of Medicine University of Washington Seattle Washington"},{"name":"Division of Genetic Medicine Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret P.","family":"Adam","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Seattle Children's Hospital Seattle Washington"},{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"LaCroix","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E. S.","family":"Leary","sequence":"additional","affiliation":[{"name":"Division of Oncology Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Laboratories Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Dobyns","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Seattle Children's Hospital Seattle Washington"},{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington"},{"name":"Center for Integrative Brain Research Seattle Children's Research Institute Seattle Washington"},{"name":"Department of Neurology University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather C.","family":"Mefford","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Seattle Children's Hospital Seattle Washington"},{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,12]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"74","article-title":"Germ\u2010line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors","volume":"59","author":"Biegel JA","year":"1999","journal-title":"Cancer 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