{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:19Z","timestamp":1786978279436,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T00:00:00Z","timestamp":1588377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008958","name":"Sanad Children's Cancer Support Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The frequency of pathogenic\/likely pathogenic (P\/LP) germline mutations in cancer\u2010related genes among children with cancer in highly consanguineous populations is not well studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole\u2010exome sequencing of germline DNA was performed in 60 children with acute leukemia. We used the St. Jude Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) data portal for the classification of germline variants by the St. Jude Medal Ceremony pipeline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010seven patients had acute lymphoblastic leukemia (ALL) and three patients had acute myeloid leukemia. Parental consanguinity was present in 27 (45%) patients. All patients were of Arab ancestry. Three patients (5%) had a history of cancer in their siblings. Five patients (8.3%) had P\/LP germline mutations in cancer\u2010related genes. Three patients with B\u2010ALL had heterozygous pathogenic mutations in\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>BRCA1<\/jats:italic>\n                      , and\n                      <jats:italic>BRCA2<\/jats:italic>\n                      ; one patient with B\u2010ALL had homozygous pathogenic mutation in\n                      <jats:italic>PMS2<\/jats:italic>\n                      ; and one patient with T\u2010ALL had LP homozygous mutation in\n                      <jats:italic>AK2<\/jats:italic>\n                      that was associated with reticular dysgenesis. Among patients who had history of parental consanguinity, three (11%) had P\/LP germline mutations compared with two (8%) in the absence of parental consanguinity. Fourteen (23%) patients had gold medal variants in cancer\u2010related genes, 13 were heterozygous, and one was homozygous. Silver medal variants were present in 35 (58%) patients; all were heterozygous except one homozygous.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Children with acute leukemia in Saudi Arabia had low frequency of P\/LP mutations in cancer\u2010related genes despite the high rate of consanguinity. Larger studies using whole\u2010genome sequencing are needed to further explore the heritability of childhood leukemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.28340","type":"journal-article","created":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T08:35:43Z","timestamp":1588408543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Frequency of pathogenic\/likely pathogenic germline variants in cancer\u2010related genes among children with acute leukemia in Saudi Arabia"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5577-3228","authenticated-orcid":false,"given":"Abdulrahman","family":"Alsultan","sequence":"first","affiliation":[{"name":"Department of Pediatrics College of Medicine King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-0796","authenticated-orcid":false,"given":"Mohammed","family":"Essa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology King Abdullah Specialist Children's Hospital  Riyadh Saudi Arabia"},{"name":"College of Medicine Ministry of National Guard Health Affairs King Saud bin Abdulaziz University for Health Sciences  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Aljefri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-1302","authenticated-orcid":false,"given":"Mouhab","family":"Ayas","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology Cancer Center King Fahad Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawaf","family":"Alkhayat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Prince Sultan Military Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Al\u2010Anzi","sequence":"additional","affiliation":[{"name":"Prince Faisal Bin Bandar Cancer Center  Qassim Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawwaz","family":"Yassin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology King Faisal Specialist Hospital and Research Center  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawaz","family":"Alkasim","sequence":"additional","affiliation":[{"name":"King Saud Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qasim","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology King Fahad Specialist Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaker","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Oncology Princess Noorah Oncology Center King Saud Bin Abdulaziz University and King Abdulaziz Medical City  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-8796","authenticated-orcid":false,"given":"Wasil","family":"Jastaniah","sequence":"additional","affiliation":[{"name":"Department of Oncology Princess Noorah Oncology Center King Saud Bin Abdulaziz University and King Abdulaziz Medical City  Jeddah Saudi Arabia"},{"name":"Department of Pediatrics Faculty of Medicine Umm Al\u2010Qura University  Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,2]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Saudi Cancer Registry MOH.Cancer Incidence and Survival Report;Saudi Arabia;2015.https:\/\/nhic.gov.sa\/eServices\/Documents\/E%20SCR%20final%206%20NOV.pdf. Accessed December 1 2019."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2018.05.006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.147"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508054"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25480"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.8589"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.146"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.250357.119"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270108"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.12.005"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj073"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0136-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.5215"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23168"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt095"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3020"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-5237"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.2203"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-745638"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06485-7"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-4268H"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP4381"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102284"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806489"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.28340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.28340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.28340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.28340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:18:39Z","timestamp":1693268319000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.28340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,2]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/pbc.28340"],"URL":"https:\/\/doi.org\/10.1002\/pbc.28340","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,2]]},"assertion":[{"value":"2020-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e28340"}}