{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:39:19Z","timestamp":1787020759914,"version":"build-2736575974"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GM2205C"],"award-info":[{"award-number":["01GM2205C"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GM1909A"],"award-info":[{"award-number":["01GM1909A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA"},{"name":"Gerdes Stiftung, Germany"},{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS2021.25"],"award-info":[{"award-number":["DKS2021.25"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Constitutional heterozygous pathogenic variants in genes coding for some components of the Fanconi anemia-BRCA 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\n                    <jats:italic>BRCA2<\/jats:italic>\n                    or\n                    <jats:italic>PALB2<\/jats:italic>\n                    . 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\n                    <jats:italic>BRCA2<\/jats:italic>\n                    pathogenic variants and medulloblastoma (MB), an embryonal tumor of the cerebellum. Median age at MB diagnosis was 32.5\u00a0months (range 7\u201358\u00a0months). 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\u00a0months, range 0\u201321\u00a0months) due to MB or other neoplasms. In conclusion, MB in patients with biallelic\n                    <jats:italic>BRCA2<\/jats:italic>\n                    pathogenic variants is a lethal disease. Future experimental treatments are necessary to help these patients.\n                  <\/jats:p>","DOI":"10.1186\/s13045-024-01547-4","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T03:02:32Z","timestamp":1714359752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Germline biallelic BRCA2 pathogenic variants and medulloblastoma: an international cohort study"],"prefix":"10.1186","volume":"17","author":[{"given":"Svenja","family":"Kastellan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Kalb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bia","family":"Sajjad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"McReynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Milde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Elbracht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Holzhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marena R.","family":"Niewisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Kratz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"1547_CR1","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1001\/jamaoncol.2022.0476","volume":"8","author":"Y Momozawa","year":"2022","unstructured":"Momozawa Y, et al. Expansion of cancer risk profile for BRCA1 and BRCA2 pathogenic variants. JAMA Oncol. 2022;8:871\u20138.","journal-title":"JAMA Oncol"},{"issue":"1","key":"1547_CR2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1200\/JCO.21.01495","volume":"40","author":"CM Dutzmann","year":"2022","unstructured":"Dutzmann CM, et al. Cancer in children with Fanconi anemia and ataxia-telangiectasia-A nationwide register-based cohort study in Germany. J Clin Oncol. 2022;40(1):32\u20139.","journal-title":"J Clin Oncol"},{"issue":"1","key":"1547_CR3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3324\/haematol.2017.178111","volume":"103","author":"BP Alter","year":"2018","unstructured":"Alter BP, et al. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up. Haematologica. 2018;103(1):30\u20139.","journal-title":"Haematologica"},{"key":"1547_CR4","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cancergen.2021.10.001","volume":"258\u2013259","author":"LJ McReynolds","year":"2021","unstructured":"McReynolds LJ, et al. Genotype-cancer association in patients with Fanconi anemia due to pathogenic variants in FANCD1 (BRCA2) or FANCN (PALB2). Cancer Genet. 2021;258\u2013259:101\u20139.","journal-title":"Cancer Genet"},{"issue":"20","key":"1547_CR5","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1093\/jnci\/djg072","volume":"95","author":"K Offit","year":"2003","unstructured":"Offit K, et al. Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. J Natl Cancer Inst. 2003;95(20):1548\u201351.","journal-title":"J Natl Cancer Inst"},{"issue":"7","key":"1547_CR6","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1182\/blood-2003-06-1970","volume":"103","author":"B Hirsch","year":"2004","unstructured":"Hirsch B, et al. Association of biallelic BRCA2\/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood. Blood. 2004;103(7):2554\u20139.","journal-title":"Blood"},{"issue":"1","key":"1547_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jmg.2006.043257","volume":"44","author":"BP Alter","year":"2007","unstructured":"Alter BP, Rosenberg PS, Brody LC. Clinical and molecular features associated with biallelic mutations in FANCD1\/BRCA2. J Med Genet. 2007;44(1):1\u20139.","journal-title":"J Med Genet"},{"key":"1547_CR8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s40364-015-0038-z","volume":"3","author":"E Miele","year":"2015","unstructured":"Miele E, et al. Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup. Biomark Res. 2015;3:13.","journal-title":"Biomark Res"},{"issue":"6","key":"1547_CR9","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S1470-2045(18)30242-0","volume":"19","author":"SM Waszak","year":"2018","unstructured":"Waszak SM, et al. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018;19(6):785\u201398.","journal-title":"Lancet Oncol"},{"issue":"3","key":"1547_CR10","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.tig.2020.11.001","volume":"37","author":"J Garcia-Lopez","year":"2021","unstructured":"Garcia-Lopez J, et al. Deconstructing sonic hedgehog medulloblastoma: molecular subtypes, drivers, and beyond. Trends Genet. 2021;37(3):235\u201350.","journal-title":"Trends Genet"},{"issue":"2","key":"1547_CR11","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30775","volume":"71","author":"S Rumley","year":"2024","unstructured":"Rumley S, Pater L. Optimization of radiotherapy in Fanconi anemia-related medulloblastoma. Pediatr Blood Cancer. 2024;71(2): e30775.","journal-title":"Pediatr Blood Cancer"},{"key":"1547_CR12","doi-asserted-by":"publisher","DOI":"10.1200\/PO.23.00221","volume":"7","author":"LR Haggstrom","year":"2023","unstructured":"Haggstrom LR, et al. Exceptional response to olaparib: a case report of metastatic esophageal squamous cell carcinoma in a patient with Fanconi Anemia, germline FANCA mutation, and somatic BRCA2 mutations. JCO Precis Oncol. 2023;7: e2300221.","journal-title":"JCO Precis Oncol"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-024-01547-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-024-01547-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-024-01547-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T03:04:19Z","timestamp":1714359859000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-024-01547-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1547"],"URL":"https:\/\/doi.org\/10.1186\/s13045-024-01547-4","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,29]]},"assertion":[{"value":"23 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Studies DRKS00017382, DRKS00007623, and NCT00027274 are IRB approved with informed cnsent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This manuscript has not been previously published and is not under consideration for publication elsewhere.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing financial interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}