[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332022-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332022-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","germline-biallelic-brca2-pathogenic-variants-and-medulloblastoma-an-international-cohort-study","Germline biallelic BRCA2 pathogenic variants and medulloblastoma - an international cohort study","","Constitutional heterozygous pathogenic variants in Fanconi anemia BRCA signaling pathway genes increase risk for common cancers, while Fanconi anemia itself is driven by germline pathogenic variants in one of 21 FA-BRCA genes and is characterized by bone marrow failure and multiple abnormalities. The highest cancer risk in Fanconi anemia occurs with biallelic pathogenic variants in BRCA2 or PALB2, yet clinical and toxicities linked to specific tumors remain limited. This international cohort study analyzes genetics, clinical course, pathology, and treatment in eight patients with Fanconi anemia due to biallelic BRCA2 variants and medulloblastoma.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/germline-biallelic-brca2-pathogenic-variants-and-medulloblastoma-an-international-cohort-study/332022/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/germline-biallelic-brca2-pathogenic-variants-and-medulloblastoma-an-international-cohort-study/332022.png","ImageObject",300,407,{"name":42,"@type":43},"Emma 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diagnosis in these patients?",{"text":72,"@type":64},"The prognosis was poor: all patients died shortly after medulloblastoma diagnosis, with median survival of 4.5 months (range 0–21 months) due to medulloblastoma or other neoplasms.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332022,1790111798,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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[https://doi.org/10.1186/s13045-024-01547-4](https://doi.org/10.1186/s13045-024-01547-4)  \nJournal of Hematology & Oncology  \n CORRESPONDENCE Open Access  \nGermline biallelic BRCA2 pathogenic variants   and medulloblastoma: an international cohort study  \nSvenja Kastellan 1, Reinhard Kalb2, Bia Sajjad3, Lisa J. McReynolds3, Neelam Giri3, David Samuel4, Till Milde5,6,7,8, Miriam Elbracht9, Susanne Holzhauer 10, Marena R. Niewisch 1† and Christian P. Kratz 1*†  \nAbstract  \nConstitutional heterozygous pathogenic variants in genes coding for some components of the Fanconi anemiaBRCA signaling pathway, which repairs DNA interstrand crosslinks, represent risk factors for common cancers, including breast, ovarian, pancreatic and prostate cancer. A high cancer risk is also a main clinical feature in patients with Fanconi anemia (FA), a rare condition characterized by bone marrow failure, endocrine and physical abnormalities. The mainly recessive condition is caused by germline pathogenic variants in one of 21 FA-BRCA pathway genes. Among patients with FA, the highest cancer risks are observed in patients with biallelic pathogenic variants in BRCA2 or PALB2 . These patients develop a range of embryonal tumors and leukemia during the first decade of life, however, little is known about specific clinical, genetic and pathologic features or toxicities. Here, we present genetic, clinical, pathological and treatment characteristics observed in an international cohort of eight patients with FA due to biallelic BRCA2 pathogenic variants and medulloblastoma (MB), an embryonal tumor of the cerebellum. Median age at MB diagnosis was 32.5 months (range 7–58 months) . All patients with available data had sonic hedgehog-MB. Six patients received chemotherapy and one patient also received proton radiation treatment. No life-threatening toxicities were documented. Prognosis was poor and all patients died shortly after MB diagnosis (median survival time 4.5 months, range 0–21 months) due to MB or other neoplasms. In conclusion, MB in patients with biallelic BRCA2 pathogenic variants is a lethal disease. Future experimental treatments are necessary to help these patients.  \nKeywords BRCA2, Fanconi anemia, Medulloblastoma  \n†Marena R. Niewisch and Christian P. Kratz contributed equally.  \n*Correspondence:  \nChristian P. Kratz [kratz.christian@mh-hannover.de](kratz.christian@mh-hannover.de)  \n1 Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany  \n2 Department of Human Genetics, University ofWürzburg, Biocenter, Würzburg, Germany  \n3 Clinical Genetics Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA  \n4 Department of Hematology-Oncology, Valley Children’s Hospital, Madera, CA, USA  \n5 Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany  \n6 Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany  \n7 Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany  \n8 National Center for Tumor Diseases (NCT), Heidelberg, Germany  \n9 Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany  \n10 Department of Pediatric Hematology and Oncology, Charité University Medicine, Berlin, Germany  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit","cbCaiqLn6h86YFZZ","https://ap.wps.com/l/cbCaiqLn6h86YFZZ","pdf",900848,"English","# Abstract\n## Background\n## Methods and cohort description\n## Key clinical findings\n## Treatment and toxicities\n## Prognosis and conclusion","[{\"question\":\"What genetic background is linked to the highest cancer risk in Fanconi anemia patients?\",\"answer\":\"Patients with Fanconi anemia who carry biallelic pathogenic variants in BRCA2 (or PALB2) show the highest observed cancer risks.\"},{\"question\":\"What medulloblastoma characteristics were reported in the eight-patient cohort?\",\"answer\":\"The cohort’s median age at medulloblastoma diagnosis was 32.5 months (range 7–58 months), and all patients with available data had sonic hedgehog medulloblastoma.\"},{\"question\":\"How did outcomes compare after medulloblastoma diagnosis in these patients?\",\"answer\":\"The prognosis was poor: all patients died shortly after medulloblastoma diagnosis, with median survival of 4.5 months (range 0–21 months) due to medulloblastoma or other neoplasms.\"}]","Germline biallelic BRCA2 pathogenic variants and medulloblastoma - an international cohort study | PDF",1789996346,13]