{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:48:29Z","timestamp":1787057309738,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T00:00:00Z","timestamp":1440115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"King Hussein Cancer Center (Intramural grant) and B.R.A.I.N child, Canada (bMMRD consortium)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"<jats:p>Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome affecting primarily individuals from consanguinous families resulting in multiple childhood cancers including high grade gliomas (HGG). This is the first study to assess the prevalence of bMMRD among patients with HGG in countries where consanguinity is high. We collected molecular and clinical information on all children diagnosed with HGG and supratentorial primitive neuroectodermal tumors (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison was made to a similar cohort from Toronto. Clinical data regarding presence of caf\u00e9 au lait macules(CAL), family history of cancer, consanguinity, pathology and treatment were collected. Tumors were centrally reviewed and tested for MMRD by immunohistochemistry of the corresponding proteins. Forty\u2010two patients fulfilled the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of whom79% also lost MMR staining in the corresponding normal cells suggestive of bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (<jats:italic>p<\/jats:italic>\u2009=\u20090.0003).The frequency of MMRD was significantly lower in Toronto cohort (23%, <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Both evidence of CAL and consanguinity correlated with bMMRD (<jats:italic>p<\/jats:italic>\u2009=\u20090.005 and 0.05,respectively) but family history of cancer didn't. HGG with all three bMMRD risk factors had evidence of MMRD and all children affected by multiple bMMRD related cancers had identical gene loss by immunohistochemical staining. In Jordan, the frequency of clinical and immunohistochemical alterations suggestive of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate counseling and cancer screening to improve survival of these patients.<\/jats:p>","DOI":"10.1002\/ijc.29724","type":"journal-article","created":{"date-parts":[[2015,8,8]],"date-time":"2015-08-08T11:32:53Z","timestamp":1439033573000},"page":"380-385","source":"Crossref","is-referenced-by-count":86,"title":["High frequency of mismatch repair deficiency among pediatric high grade gliomas in <scp>J<\/scp>ordan"],"prefix":"10.1002","volume":"138","author":[{"given":"Nisreen","family":"Amayiri","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hematology\/Oncology King Hussein Cancer Center Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Tabori","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Institute of Medical Sciences the University of Toronto Toronto Canada"},{"name":"Department of Pediatrics The Hospital for Sick Children, Institute of Medical Sciences, the University of Toronto Toronto Canada"},{"name":"Arthur and Sonia Labbatt Brain Tumor Research Center Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Institute of Medical Sciences the University of Toronto Toronto Canada"},{"name":"Department of Pediatrics The Hospital for Sick Children, Institute of Medical Sciences, the University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doua","family":"Bakry","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Institute of Medical Sciences the University of Toronto Toronto Canada"},{"name":"Department of Pediatrics The Hospital for Sick Children, Institute of Medical Sciences, the University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melyssa","family":"Aronson","sequence":"additional","affiliation":[{"name":"The Familial Gastrointestinal Cancer Registry at the Zane Cohen Centre for Digestive Disease and Department of Surgery Mount Sinai Hospital Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Durno","sequence":"additional","affiliation":[{"name":"The Familial Gastrointestinal Cancer Registry at the Zane Cohen Centre for Digestive Disease and Department of Surgery Mount Sinai Hospital Toronto Canada"},{"name":"Division of Gastroenterology, Nutrition and Hepatology The Hospital for Sick Children Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rakopoulos","sequence":"additional","affiliation":[{"name":"Division of Pathology, Arthur and Sonia Labatt Brain Tumour Research Center The Hospital for Sick Children Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Malkin","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Institute of Medical Sciences the University of Toronto Toronto Canada"},{"name":"Department of Pediatrics The Hospital for Sick Children, Institute of Medical Sciences, the University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Qaddoumi","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awni","family":"Musharbash","sequence":"additional","affiliation":[{"name":"Department of Surgery King Hussein Cancer Center Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisa","family":"Swaidan","sequence":"additional","affiliation":[{"name":"Department of Radiology King Hussein Cancer Center Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bouffet","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, The Hospital for Sick Children, Institute of Medical Sciences the University of Toronto Toronto Canada"},{"name":"Department of Pediatrics The Hospital for Sick Children, Institute of Medical Sciences, the University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Division of Pathology, Arthur and Sonia Labatt Brain Tumour Research Center The Hospital for Sick Children Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysa","family":"Al\u2010Hussaini","sequence":"additional","affiliation":[{"name":"Department of Pathology King Hussein Cancer Center Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of BMMRD 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