{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T13:19:48Z","timestamp":1794489588911,"version":"4.9.1"},"reference-count":85,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inherited predisposition to myeloid malignancies is more common than previously appreciated. We analyzed the whole-exome sequencing data of paired leukemia and skin biopsy samples from 391 adult patients from the Beat AML 1.0 consortium. Using the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines for variant interpretation, we curated 1547 unique variants from 228 genes. The pathogenic\/likely pathogenic (P\/LP) germline variants were identified in 53 acute myeloid leukemia (AML) patients (13.6%) in 34 genes, including 6.39% (25\/391) of patients harboring P\/LP variants in genes considered clinically actionable (tier 1). 41.5% of the 53 patients with P\/LP variants were in genes associated with the DNA damage response. The most frequently mutated genes were CHEK2 (8 patients) and DDX41 (7 patients). Pathogenic germline variants were also found in new candidate genes (DNAH5, DNAH9, DNMT3A, and SUZ12). No strong correlation was found between the germline mutational rate and age of AML onset. Among 49 patients who have a reported history of at least one family member affected with hematological malignancies, 6 patients harbored known P\/LP germline variants and the remaining patients had at least one variant of uncertain significance, suggesting a need for further functional validation studies. Using CHEK2 as an example, we show that three-dimensional protein modeling can be one of the effective methodologies to prioritize variants of unknown significance for functional studies. Further, we evaluated an in silico approach that applies ACMG curation in an automated manner using the tool for assessment and (TAPES) prioritization in exome studies, which can minimize manual curation time for variants. Overall, our findings suggest a need to comprehensively understand the predisposition potential of many germline variants in order to enable closer monitoring for disease management and treatment interventions for affected patients and families.<\/jats:p>","DOI":"10.1182\/blood.2021011354","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T16:26:41Z","timestamp":1630945601000},"page":"1208-1221","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":101,"title":["Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML"],"prefix":"10.1182","volume":"139","author":[{"given":"Fei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-8167","authenticated-orcid":false,"given":"Nicola","family":"Long","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-5235","authenticated-orcid":false,"given":"Tauangtham","family":"Anekpuritanang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bottomly","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Division of Bioinformatics & Computational Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Savage","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-8200","authenticated-orcid":false,"given":"Tiffany","family":"Lee","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Solis-Ruiz","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Borate","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Wilmot","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Division of Bioinformatics & Computational Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tognon","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Bock","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado, Aurora, CO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6519-4860","authenticated-orcid":false,"given":"Daniel A.","family":"Pollyea","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado, Aurora, CO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikripa","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinidhi","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prapti","family":"Patel","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Collins","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Tantravahi","sequence":"additional","affiliation":[{"name":"University of Utah Huntsman Cancer Institute, Salt Lake City, UT; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Deininger","sequence":"additional","affiliation":[{"name":"University of Utah Huntsman Cancer Institute, Salt Lake City, UT; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8331-8206","authenticated-orcid":false,"given":"Brian","family":"Druker","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujwal","family":"Shinde","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Tyner","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Department of Cell, Developmental & Cancer Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-5144","authenticated-orcid":false,"given":"Richard D.","family":"Press","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"McWeeney","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Division of Bioinformatics & Computational Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8319-6162","authenticated-orcid":false,"given":"Anupriya","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR;"},{"name":"Department of Cell, Developmental & Cancer Biology,"},{"name":"Division of Hematology and Oncology, and"},{"name":"Division of Oncological Sciences, Oregon Health & Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"12","key":"2022022416211595500_B1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute myeloid leukemia","volume":"373","author":"D\u00f6hner","year":"2015","journal-title":"N Engl J Med."},{"key":"2022022416211595500_B2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1182\/asheducation-2016.1.302","article-title":"Germ line mutations associated with leukemias","volume":"2016","author":"Porter","year":"2016","journal-title":"Hematology Am Soc Hematol Educ Program."},{"issue":"4","key":"2022022416211595500_B3","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1177\/2040620713498161","article-title":"Genetic predispositions to childhood leukemia","volume":"4","author":"Stieglitz","year":"2013","journal-title":"Ther Adv Hematol."},{"issue":"2","key":"2022022416211595500_B4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/13793","article-title":"Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia","volume":"23","author":"Song","year":"1999","journal-title":"Nat Genet."},{"issue":"10","key":"2022022416211595500_B5","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1038\/s41375-018-0049-5","article-title":"Germline alterations in a consecutive series of acute myeloid leukemia","volume":"32","author":"Wartiovaara-Kautto","year":"2018","journal-title":"Leukemia."},{"issue":"4","key":"2022022416211595500_B6","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2017-02-735290","article-title":"Genetic predisposition to hematologic malignancies: management and surveillance","volume":"130","author":"Godley","year":"2017","journal-title":"Blood."},{"issue":"7","key":"2022022416211595500_B7","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1182\/blood-2017-09-806489","article-title":"A landscape of germ line mutations in a cohort of inherited bone marrow failure patients","volume":"131","author":"Bluteau","year":"2018","journal-title":"Blood."},{"issue":"20","key":"2022022416211595500_B8","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia [published correction appears in Blood. 2016;128(3):462-463]","volume":"127","author":"Arber","year":"2016","journal-title":"Blood."},{"key":"2022022416211595500_B9","volume-title":"International Agency for Research on C, World Health O. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.","author":"Swerdlow","year":"2017."},{"issue":"4","key":"2022022416211595500_B10","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"D\u00f6hner","year":"2017","journal-title":"Blood."},{"key":"2022022416211595500_B11","author":"Network"},{"issue":"19","key":"2022022416211595500_B12","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1182\/blood-2010-12-326322","article-title":"First report of multiple CEBPA mutations contributing to donor origin of leukemia relapse after allogeneic hematopoietic stem cell transplantation","volume":"117","author":"Xiao","year":"2011","journal-title":"Blood."},{"issue":"2","key":"2022022416211595500_B13","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/leu.2016.310","article-title":"Re-emergence of acute myeloid leukemia in donor cells following allogeneic transplantation in a family with a germline DDX41 mutation","volume":"31","author":"Berger","year":"2017","journal-title":"Leukemia."},{"issue":"7728","key":"2022022416211595500_B14","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41586-018-0623-z","article-title":"Functional genomic landscape of acute myeloid leukaemia","volume":"562","author":"Tyner","year":"2018","journal-title":"Nature."},{"issue":"12","key":"2022022416211595500_B15","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.3390\/cells9122675","article-title":"CHEK2 germline variants in cancer predisposition: stalemate rather than checkmate","volume":"9","author":"Stolarova","year":"2020","journal-title":"Cells."},{"issue":"4","key":"2022022416211595500_B16","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: an ensemble method for predicting the pathogenicity of rare missense variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am J Hum Genet."},{"issue":"D1","key":"2022022416211595500_B17","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"2022022416211595500_B18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"issue":"10","key":"2022022416211595500_B19","doi-asserted-by":"crossref","first-page":"e1007453","DOI":"10.1371\/journal.pcbi.1007453","article-title":"TAPES: a tool for assessment and prioritisation in exome studies","volume":"15","author":"Xavier","year":"2019","journal-title":"PLOS Comput Biol."},{"issue":"5","key":"2022022416211595500_B20","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1182\/blood-2016-01-693879","article-title":"Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia","volume":"128","author":"Metzeler","year":"2016","journal-title":"Blood."},{"issue":"23","key":"2022022416211595500_B21","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic classification and prognosis in acute myeloid leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N Engl J Med."},{"issue":"8","key":"2022022416211595500_B22","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1182\/blood-2015-10-676098","article-title":"Novel germ line DDX41 mutations define families with a lower age of MDS\/AML onset and lymphoid malignancies","volume":"127","author":"Lewinsohn","year":"2016","journal-title":"Blood."},{"issue":"10","key":"2022022416211595500_B23","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/leu.2016.124","article-title":"Germline heterozygous DDX41 variants in a subset of familial myelodysplasia and acute myeloid leukemia","volume":"30","author":"Cardoso","year":"2016","journal-title":"Leukemia."},{"issue":"17","key":"2022022416211595500_B24","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1182\/blood.2019000909","article-title":"Germline DDX41 mutations define a significant entity within adult MDS\/AML patients","volume":"134","author":"S\u00e9bert","year":"2019","journal-title":"Blood."},{"issue":"6","key":"2022022416211595500_B25","doi-asserted-by":"crossref","first-page":"890","DOI":"10.3324\/haematol.2011.054361","article-title":"Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival","volume":"97","author":"B\u00f6d\u00f6r","year":"2012","journal-title":"Haematologica."},{"issue":"10","key":"2022022416211595500_B26","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/ng.913","article-title":"Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia","volume":"43","author":"Hahn","year":"2011","journal-title":"Nat Genet."},{"issue":"10","key":"2022022416211595500_B27","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1182\/blood-2016-02-698951","article-title":"Cooperation of germ line JAK2 mutations E846D and R1063H in hereditary erythrocytosis with megakaryocytic atypia","volume":"128","author":"Kapralova","year":"2016","journal-title":"Blood."},{"issue":"2","key":"2022022416211595500_B28","doi-asserted-by":"crossref","first-page":"e0148793","DOI":"10.1371\/journal.pone.0148793","article-title":"Robust DNA damage response and elevated reactive oxygen species in TINF2-mutated dyskeratosis congenita cells","volume":"11","author":"Pereboeva","year":"2016","journal-title":"PLoS One."},{"issue":"2","key":"2022022416211595500_B29","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ng1156","article-title":"Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia [published correction appears in Nat. Genet. 2003;34:148-150]","volume":"34","author":"Tartaglia","year":"2003","journal-title":"Nat Genet."},{"issue":"4","key":"2022022416211595500_B30","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/ajmg.a.38108","article-title":"Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature","volume":"173","author":"Siegfried","year":"2017","journal-title":"Am J Med Genet A."},{"issue":"1","key":"2022022416211595500_B31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1182\/blood.V92.1.267.413a31_267_272","article-title":"Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1","volume":"92","author":"Side","year":"1998","journal-title":"Blood."},{"issue":"6","key":"2022022416211595500_B32","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1055\/s-0031-1291377","article-title":"Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment","volume":"37","author":"Ballmaier","year":"2011","journal-title":"Semin Thromb Hemost."},{"issue":"2","key":"2022022416211595500_B33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s40291-018-0368-2","article-title":"Shwachman-Diamond syndrome: molecular mechanisms and current perspectives","volume":"23","author":"Bezzerri","year":"2019","journal-title":"Mol Diagn Ther."},{"key":"2022022416211595500_B34","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3389\/fendo.2017.00235","article-title":"Identification of MPL R102P mutation in hereditary thrombocytosis","volume":"8","author":"Bellann\u00e9-Chantelot","year":"2017","journal-title":"Front Endocrinol (Lausanne)."},{"key":"2022022416211595500_B35","volume-title":"GeneReviews\u00ae [Internet]","author":"Mehta","year":"1993\u20132021"},{"key":"2022022416211595500_B36","volume-title":"GeneReviews\u00ae [Internet].","author":"Gatti","year":"1993\u20132021"},{"key":"2022022416211595500_B37","volume-title":"GeneReviews\u00ae [Internet].","author":"Varon","year":"1993\u20132021"},{"issue":"2","key":"2022022416211595500_B38","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/ijc.1329","article-title":"Cancer risk in heterozygotes for ataxia-telangiectasia","volume":"93","author":"Geoffroy-Perez","year":"2001","journal-title":"Int J Cancer."},{"issue":"11","key":"2022022416211595500_B39","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/jnci\/dji141","article-title":"Cancer risks and mortality in heterozygous ATM mutation carriers","volume":"97","author":"Thompson","year":"2005","journal-title":"J Natl Cancer Inst."},{"issue":"11","key":"2022022416211595500_B40","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1038\/ng1902","article-title":"Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles","volume":"38","author":"Seal","year":"2006","journal-title":"Nat Genet."},{"issue":"19","key":"2022022416211595500_B41","doi-asserted-by":"crossref","first-page":"9591","DOI":"10.1158\/0008-5472.CAN-07-1501","article-title":"Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer","volume":"67","author":"Berwick","year":"2007","journal-title":"Cancer Res."},{"issue":"6","key":"2022022416211595500_B42","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/gcc.22448","article-title":"Candidate susceptibility variants for esophageal squamous cell carcinoma","volume":"56","author":"Donner","year":"2017","journal-title":"Genes Chromosomes Cancer."},{"issue":"12","key":"2022022416211595500_B43","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/ng1671","article-title":"Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR","volume":"37","author":"Bell","year":"2005","journal-title":"Nat Genet."},{"issue":"5","key":"2022022416211595500_B44","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/s41375-018-0074-4","article-title":"SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies","volume":"32","author":"Davidsson","year":"2018","journal-title":"Leukemia."},{"issue":"21","key":"2022022416211595500_B45","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1182\/blood-2017-05-787390","article-title":"Germline loss-of-function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes","volume":"132","author":"Nagata","year":"2018","journal-title":"Blood."},{"issue":"3","key":"2022022416211595500_B46","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ccr.2013.08.011","article-title":"Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7","volume":"24","author":"Nagamachi","year":"2013","journal-title":"Cancer Cell."},{"issue":"6","key":"2022022416211595500_B47","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.molcel.2009.09.007","article-title":"Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase","volume":"35","author":"Cai","year":"2009","journal-title":"Mol Cell."},{"issue":"26","key":"2022022416211595500_B48","doi-asserted-by":"crossref","first-page":"19154","DOI":"10.1074\/jbc.M112.442681","article-title":"The mechanism by which a propeptide-encoded pH sensor regulates spatiotemporal activation of furin","volume":"288","author":"Williamson","year":"2013","journal-title":"J Biol Chem."},{"issue":"12","key":"2022022416211595500_B49","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1093\/hmg\/dds101","article-title":"Response to DNA damage of CHEK2 missense mutations in familial breast cancer","volume":"21","author":"Roeb","year":"2012","journal-title":"Hum Mol Genet."},{"issue":"8","key":"2022022416211595500_B50","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/humu.20321","article-title":"Characterization of CHEK2 mutations in prostate cancer","volume":"27","author":"Wu","year":"2006","journal-title":"Hum Mutat."},{"issue":"5","key":"2022022416211595500_B51","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/humu.23728","article-title":"Functional characterization of CHEK2 variants in a\u00a0Saccharomyces cerevisiae\u00a0system","volume":"40","author":"Delimitsou","year":"2019","journal-title":"Hum Mutat."},{"issue":"8","key":"2022022416211595500_B52","doi-asserted-by":"crossref","first-page":"e3062","DOI":"10.1371\/journal.pone.0003062","article-title":"CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer","volume":"3","author":"Chrisanthar","year":"2008","journal-title":"PLoS One."},{"issue":"18","key":"2022022416211595500_B53","doi-asserted-by":"crossref","first-page":"8966","DOI":"10.1158\/0008-5472.CAN-06-1990","article-title":"Rare germ line CHEK2 variants identified in breast cancer families encode proteins that show impaired activation","volume":"66","author":"Sodha","year":"2006","journal-title":"Cancer Res."},{"issue":"44","key":"2022022416211595500_B54","doi-asserted-by":"crossref","first-page":"18032","DOI":"10.1073\/pnas.1115052108","article-title":"Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing","volume":"108","author":"Walsh","year":"2011","journal-title":"Proc Natl Acad Sci USA."},{"issue":"4","key":"2022022416211595500_B55","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1074\/jbc.M009727200","article-title":"Characterization of tumor-associated Chk2 mutations","volume":"276","author":"Wu","year":"2001","journal-title":"J Biol Chem."},{"issue":"5","key":"2022022416211595500_B56","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S1097-2765(02)00527-0","article-title":"Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2","volume":"9","author":"Li","year":"2002","journal-title":"Mol Cell."},{"issue":"39","key":"2022022416211595500_B57","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.1038\/sj.onc.1204811","article-title":"Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway","volume":"20","author":"Falck","year":"2001","journal-title":"Oncogene."},{"issue":"6830","key":"2022022416211595500_B58","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/35071124","article-title":"The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis","volume":"410","author":"Falck","year":"2001","journal-title":"Nature."},{"issue":"4","key":"2022022416211595500_B59","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/ijc.20299","article-title":"CHEK2 variant I157T may be associated with increased breast cancer risk","volume":"111","author":"Kilpivaara","year":"2004","journal-title":"Int J Cancer."},{"issue":"5","key":"2022022416211595500_B60","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1038\/leu.2017.28","article-title":"Clinical utility of gene panel-based testing for hereditary myelodysplastic syndrome\/acute leukemia predisposition syndromes","volume":"31","author":"Guidugli","year":"2017","journal-title":"Leukemia."},{"issue":"24","key":"2022022416211595500_B61","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","article-title":"Germline mutations in predisposition genes in pediatric cancer","volume":"373","author":"Zhang","year":"2015","journal-title":"N Engl J Med."},{"issue":"22","key":"2022022416211595500_B62","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1182\/blood-2015-04-641100","article-title":"Genomic analysis of germ line and somatic variants in familial myelodysplasia\/acute myeloid leukemia","volume":"126","author":"Churpek","year":"2015","journal-title":"Blood."},{"issue":"7","key":"2022022416211595500_B63","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.clml.2016.04.001","article-title":"Evaluation of patients and families with concern for predispositions to hematologic malignancies within the Hereditary Hematologic Malignancy Clinic (HHMC)","volume":"16","author":"DiNardo","year":"2016","journal-title":"Clin Lymphoma Myeloma Leuk."},{"key":"2022022416211595500_B64","article-title":"Prevalence of Inherited Cancer Predisposition Mutations in a Cohort of Older AML Patients Enrolled on the Beat AML Master Trial","volume-title":"Blood","author":"Borate","year":"2019"},{"issue":"5","key":"2022022416211595500_B65","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/bjh.14713","article-title":"Advances in understanding the pathogenesis of familial myeloproliferative neoplasms","volume":"178","author":"Rumi","year":"2017","journal-title":"Br J Haematol."},{"issue":"1","key":"2022022416211595500_B66","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/s41467-020-14829-5","article-title":"The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants","volume":"11","author":"Rio-Machin","year":"2020","journal-title":"Nat Commun."},{"issue":"5","key":"2022022416211595500_B67","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/15592294.2020.1809871","article-title":"Germline DNMT3A mutation in familial acute myeloid leukaemia","volume":"16","author":"DiNardo","year":"2021","journal-title":"Epigenetics."},{"issue":"2","key":"2022022416211595500_B68","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1158\/1055-9965.EPI-05-0557","article-title":"The CHEK2*1100delC allelic variant and risk of breast cancer: screening results from the Breast Cancer Family Registry","volume":"15","author":"Bernstein","year":"2006","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"issue":"1","key":"2022022416211595500_B69","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1200\/JCO.2005.05.5160","article-title":"Increased risk of breast cancer associated with CHEK2*1100delC","volume":"25","author":"Weischer","year":"2007","journal-title":"J Clin Oncol."},{"issue":"11","key":"2022022416211595500_B70","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1200\/JCO.2015.63.3594","article-title":"Increased risk for other cancers in addition to breast cancer for CHEK2*1100delC heterozygotes estimated from the Copenhagen General Population Study","volume":"34","author":"N\u00e4slund-Koch","year":"2016","journal-title":"J Clin Oncol."},{"issue":"9","key":"2022022416211595500_B71","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1084\/jem.20122842","article-title":"DNA repair genes are selectively mutated in diffuse large B cell lymphomas","volume":"210","author":"de Miranda","year":"2013","journal-title":"J Exp Med."},{"issue":"10","key":"2022022416211595500_B72","doi-asserted-by":"crossref","first-page":"e0140819","DOI":"10.1371\/journal.pone.0140819","article-title":"Association of germline CHEK2 gene variants with risk and prognosis of non-Hodgkin lymphoma","volume":"10","author":"Havranek","year":"2015","journal-title":"PLoS One."},{"key":"2022022416211595500_B73","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.leukres.2018.05.013","article-title":"Constitutional mutations of the CHEK2 gene are a risk factor for MDS, but not for\u00a0de novo AML","volume":"70","author":"Janiszewska","year":"2018","journal-title":"Leuk Res."},{"issue":"2","key":"2022022416211595500_B74","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/cncr.29615","article-title":"Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia","volume":"122","author":"Churpek","year":"2016","journal-title":"Cancer."},{"key":"2022022416211595500_B75","doi-asserted-by":"crossref","DOI":"10.1038\/s41375-021-01246-w","article-title":"Targeted gene panels identify a high frequency of pathogenic germline variants \u00a0in patients diagnosed with a hematological malignancy and at least one other independent cancer","author":"Singhal","year":"2021","journal-title":"Leukemia."},{"issue":"9","key":"2022022416211595500_B76","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1158\/0008-5472.CAN-13-3608","article-title":"SWI\/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein stability","volume":"74","author":"Watanabe","year":"2014","journal-title":"Cancer Res."},{"issue":"3","key":"2022022416211595500_B77","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1080\/08916934.2018.1454912","article-title":"SAMHD1: recurring roles in cell cycle, viral restriction, cancer, and innate immunity","volume":"51","author":"Mauney","year":"2018","journal-title":"Autoimmunity."},{"issue":"4","key":"2022022416211595500_B78","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.currproblcancer.2017.02.009","article-title":"Inherited mutations in DNA repair genes and cancer risk","volume":"41","author":"Romero-Laorden","year":"2017","journal-title":"Curr Probl Cancer."},{"issue":"3","key":"2022022416211595500_B79","first-page":"597","article-title":"A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer","volume":"55","author":"Lang","year":"2019","journal-title":"Int J Oncol."},{"issue":"3","key":"2022022416211595500_B80","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3390\/cancers11030352","article-title":"BRCA2 and other DDR genes in prostate cancer","volume":"11","author":"Nombela","year":"2019","journal-title":"Cancers (Basel)."},{"key":"2022022416211595500_B81","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1182\/blood-2019-126462","article-title":"Deleterious germline variants, especially in the DNA repair pathway, are common in patients with non-related multiple cancers, one of them being hematological malignancy","volume":"134","author":"Singhal","year":"2019","journal-title":"Blood."},{"issue":"8","key":"2022022416211595500_B82","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.6004\/jnccn.2017.0133","article-title":"DNA repair dysfunction in pancreatic cancer: a clinically relevant subtype for drug development","volume":"15","author":"Golan","year":"2017","journal-title":"J Natl Compr Canc Netw."},{"issue":"4","key":"2022022416211595500_B83","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3324\/haematol.12234","article-title":"Cancer\u00a0risks in Fanconi anemia: findings from the German Fanconi Anemia Registry","volume":"93","author":"Rosenberg","year":"2008","journal-title":"Haematologica."},{"issue":"11","key":"2022022416211595500_B84","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/j.jmb.2019.04.009","article-title":"Can\u00a0predicted protein 3D structures provide reliable insights into whether missense variants are disease associated?","volume":"431","author":"Ittisoponpisan","year":"2019","journal-title":"J Mol Biol."},{"key":"2022022416211595500_B85","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fped.2017.00252","article-title":"Clinical assessment and diagnosis of germline predisposition to hematopoietic malignancies: the University of Chicago experience","volume":"5","author":"Desai","year":"2017","journal-title":"Front Pediatr."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/8\/1208\/1874927\/bloodbld2021011354.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/8\/1208\/1874927\/bloodbld2021011354.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T11:26:39Z","timestamp":1645701999000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/139\/8\/1208\/476792\/Identification-and-prioritization-of-myeloid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,24]]},"references-count":85,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,2,24]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2021011354","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,24]]}}}