{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T14:45:52Z","timestamp":1772030752865,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T00:00:00Z","timestamp":1706400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In 2002, heterozygous suppressor of fused variants (<jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin\u2010Goltz syndrome; OMIM 109400), an autosomal\u2010dominant cancer predisposition syndrome. The phenotype of patients with germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variants is very poorly characterized due to a paucity of large studies with long\u2010term follow\u2010up. As such, there is a clinical need to better characterize the spectrum of neoplasms among patients with germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variants so that clinicians can provide accurate counseling and optimize tumor surveillance strategies. The objective of this study is to perform a scoping review to map the evidence on the rate of medulloblastoma and to describe the spectrum of other neoplasms among patients with germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variants. A review of all published literature in PubMed (MEDLINE), EMBASE, Cochrane, and Web of Science were searched from the beginning of each respective database until October 9, 2021. Studies of pediatric and adult patients with a confirmed germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variant who were evaluated for the presence of any neoplasm (benign or malignant) were included. There were 176 patients (<jats:italic>N<\/jats:italic>\u2009=\u200930 studies) identified with a confirmed germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variant who met inclusion criteria. Data were extracted from two cohort studies, two case\u2010control studies, 18 case series, and eight case reports. The median age at diagnosis of a germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variant was 4.5\u2009years where 44.4% identified as female and 13.4% of variants were de novo. There were 34 different neoplasms (benign and malignant) documented among patients with confirmed germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variants, and the most common were medulloblastoma (<jats:italic>N<\/jats:italic>\u2009=\u200959 patients), BCC (<jats:italic>N<\/jats:italic>\u2009=\u200921 patients), and meningioma (<jats:italic>N<\/jats:italic>\u2009=\u200919 patients). The median age at medulloblastoma diagnosis was 1.42\u2009years (range 0.083\u20133; interquartile range 1.2). When data were available for these three most frequent neoplasms (<jats:italic>N<\/jats:italic>\u2009=\u200995 patients), 31 patients (32.6%) had neither MB, BCC nor meningioma; 51 patients (53.7%) had one of medulloblastoma or BCC or meningioma; eight patients (8.4%) had two of medulloblastoma or BCC or meningioma, and five patients (5.3%) had medulloblastoma and BCC and meningioma. This is the first study to synthesize the data on the frequency and spectrum of neoplasms specifically among patients with a confirmed germline <jats:italic>SUFU<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> variant. This scoping review is a necessary step forward in optimizing evidence\u2010based tumor surveillance strategies for medulloblastoma and estimating the risk of other neoplasms that could impact patient outcomes.<\/jats:p>","DOI":"10.1002\/ajmg.a.63496","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T05:33:16Z","timestamp":1706506396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Medulloblastoma and other neoplasms in patients with heterozygous germline <scp><i>SUFU<\/i><\/scp> variants: A scoping review"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1784-4789","authenticated-orcid":false,"given":"Stephanie G.","family":"Lee","sequence":"first","affiliation":[{"name":"Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Li Ka Shing Knowledge Institute St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomic Science, Manchester Centre for Genomic Medicine, Manchester Academic Health Science Centre University of Manchester, Manchester NHS Foundation Trust  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maddie","family":"Stephen","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Goren","sequence":"additional","affiliation":[{"name":"Queen's School of Medicine Queens University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Bondy","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2018.1435111"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/CNCR.11537"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9650184"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/AJMG.A.34128"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.067751"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.7258"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCELL.2017.05.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00403-013-1357-2"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1991.435"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.6.460"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104669"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0247-7"},{"key":"e_1_2_9_15_1","unstructured":"Female Breast Cancer. 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