{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:31:08Z","timestamp":1776209468568,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Germline TP53 variants represent a main genetic cause of breast cancers before 31 years of age. Development of cancer multi-gene panels has resulted in an exponential increase of germline TP53 testing in breast cancer patients. Interpretation of TP53 variants, which are mostly missense, is complex and requires excluding clonal haematopoiesis and circulating tumour DNA. In breast cancer patients harbouring germline disease-causing TP53 variants, radiotherapy contributing to the development of subsequent tumours should be, if possible, avoided and, within families, annual follow-up including whole-body MRI should be offered to carriers. We consider that, in breast cancer patients, germline TP53 testing should be performed before treatment and offered systematically only to patients with: (i) invasive breast carcinoma or ductal carcinoma in situ (DCIS) before 31; or (ii) bilateral or multifocal or HER2+ invasive breast carcinoma\/DCIS or phyllode tumour before 36; or (iii) invasive breast carcinoma before 46 and another TP53 core tumour (breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumour, adrenocortical carcinoma); or (iv) invasive breast carcinoma before 46 and one first- or second-degree relative with a TP53 core tumour before 56. In contrast, women presenting with breast cancer after 46, without suggestive personal or familial history, should not be tested for TP53.<\/jats:p>","DOI":"10.3390\/cancers12123762","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T22:30:52Z","timestamp":1607985052000},"page":"3762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Germline TP53 Testing in Breast Cancers: Why, When and How?"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5784","authenticated-orcid":false,"given":"D. Gareth","family":"Evans","sequence":"first","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, University of Manchester, Manchester M13 9WL, UK"},{"name":"Manchester Centre for Genomic Medicine St Mary\u2019s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6297-2855","authenticated-orcid":false,"given":"Emma R.","family":"Woodward","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, University of Manchester, Manchester M13 9WL, UK"},{"name":"Manchester Centre for Genomic Medicine St Mary\u2019s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK"}]},{"given":"Svetlana","family":"Bajalica-Lagercrantz","sequence":"additional","affiliation":[{"name":"Hereditary Cancer Unit, Department of Clinical Genetics, Karolinska University Hospital, SE-17176 Stockholm, Sweden"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-2264","authenticated-orcid":false,"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup-Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Porto Comprehensive Cancer Center, 4200-072 Porto, Portugal"}]},{"given":"Thierry","family":"Frebourg","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, 76000 Rouen, France"},{"name":"Inserm U1245, Normandie University, UNIROUEN, Normandy Centre for Genomic and Personalized Medicine, 76183 Rouen, France"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1126\/science.1978757","article-title":"Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms","volume":"250","author":"Malkin","year":"1990","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/348747a0","article-title":"Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome","volume":"348","author":"Srivastava","year":"1990","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"747","DOI":"10.7326\/0003-4819-71-4-747","article-title":"Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?","volume":"71","author":"Li","year":"1969","journal-title":"Ann. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0306-9877(79)90059-8","article-title":"Childhood cancer and the SBLA syndrome","volume":"5","author":"Lynch","year":"1979","journal-title":"Med. Hypotheses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1086\/302575","article-title":"Are there low-penetrance TP53 Alleles? Evidence from childhood adrenocortical tumors","volume":"65","author":"Varley","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1200\/JCO.2009.26.8169","article-title":"TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors","volume":"28","author":"Tabori","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/pbc.24223","article-title":"Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: A population-based survey","volume":"59","author":"Magnusson","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/cncr.28507","article-title":"Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers","volume":"120","author":"Hettmer","year":"2014","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/sj.bjc.6605606","article-title":"Long-term outcomes of breast cancer in women aged 30 years or younger, based on family history, pathology and BRCA1\/BRCA2\/TP53 status","volume":"102","author":"Evans","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_10","first-page":"250","article-title":"Beyond Li Fraumeni Syndrome: Clinical characteristics of families with p53 germline mutations","volume":"7","author":"Gonzalez","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1136\/jmg.2009.073429","article-title":"TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: Mutation detection rate and relative frequency of cancers in different familial phenotypes","volume":"47","author":"Ruijs","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1200\/JCO.2014.59.5728","article-title":"Revisiting Li-Fraumeni Syndrome from TP53 Mutation Carriers","volume":"33","author":"Bougeard","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1136\/jmedgenet-2017-104976","article-title":"Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome","volume":"55","author":"Charbonnier","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41431-020-0638-4","article-title":"Guidelines for the Li-Fraumeni and heritable TP53-related cancer syndromes","volume":"28","author":"Frebourg","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_15","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."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8424","DOI":"10.1073\/pnas.1431692100","article-title":"Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein byhigh-resolution missense mutation analysis","volume":"100","author":"Kato","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.molcel.2018.06.012","article-title":"A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation","volume":"71","author":"Kotler","year":"2018","journal-title":"Mol. Cell."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s41588-018-0204-y","article-title":"Mutational processes shape the landscape of TP53 mutations in human cancer","volume":"50","author":"Giacomelli","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/humu.23035","article-title":"TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data","volume":"37","author":"Bouaoun","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Raad, S., Rolain, M., Coutant, S., Derambure, C., Lanos, R., Charbonnier, F., Bou, J., Bouvignies, E., Lienard, G., and Vasseur, S. (2020). A blood functional assay for rapid clinical interpretation of germline TP53 variants. J. Med. Genet.","DOI":"10.1136\/jmedgenet-2020-107059"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fortuno, C., Lee, K., Olivier, M., and Pesaran, T. (2020). Germline TP53 variants. Specifications of the ACMG\/AMP variant interpretation guidelines for germline TP53 variants. Hum. Mutat., in press.","DOI":"10.1101\/2020.04.25.20078931"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/humu.23673","article-title":"Variable population prevalence estimates of germline TP53 variants: A gnomAD-based analysis","volume":"40","author":"Frone","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1002\/humu.23750","article-title":"Concern regarding classification of germline TP53 variants as likely pathogenic","volume":"40","author":"Evans","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/S0140-6736(03)12856-5","article-title":"Early Onset Breast Cancer Study Group. Prediction of pathogenic mutations in patients with early-onset breast cancer by family history","volume":"361","author":"Lalloo","year":"2003","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/s41431-020-00710-y","article-title":"Reply to Kratz et al","volume":"28","author":"Frebourg","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/jamaoncol.2015.0197","article-title":"Germline TP53 mutations in patients with early-onset colorectal cancer in the colon cancer family registry","volume":"1","author":"Yurgelun","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41436-019-0598-7","article-title":"Incidence of mosaicism in 1055 de novo NF2 cases: Much higher than previous estimates with high utility of next-generation sequencing","volume":"22","author":"Evans","year":"2020","journal-title":"Genet. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/gim.2017.196","article-title":"Somatic TP53 variants frequently confound germ-line testing results","volume":"20","author":"Weitzel","year":"2018","journal-title":"Genet. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1002\/humu.23653","article-title":"Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from clonal hematopoiesis: Results of the observational AGO-TR1 trial","volume":"39","author":"Harter","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/MOH.0000000000000509","article-title":"p53 involvement in clonal hematopoiesis of indeterminate potential","volume":"4","author":"Chen","year":"2019","journal-title":"Curr. Opin. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13058-019-1193-1","article-title":"Li-Fraumeni syndrome: Not a straightforward diagnosis anymore-the interpretation of pathogenic variants of low allele frequency and the differences between germline PVs, mosaicism, and clonal hematopoiesis","volume":"21","author":"Batalini","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.ajog.2005.01.054","article-title":"Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer","volume":"193","author":"Swisher","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_34","first-page":"1932","article-title":"P53 germline mutations in childhood cancers and cancer risk for carrier individuals","volume":"82","author":"Chompret","year":"2000","journal-title":"Br. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1002\/cncr.30248","article-title":"Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort","volume":"122","author":"Mai","year":"2016","journal-title":"Cancer."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/CCO.0000000000000423","article-title":"Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: Temporal phases of Li-Fraumeni syndrome","volume":"30","author":"Amadou","year":"2018","journal-title":"Curr. Opin. Oncol."},{"key":"ref_37","unstructured":"Dorling, L., Carvalho, S., and Allen, J. (2020). Breast cancer risk genes: Association analysis of rare coding variants in 34 genes in 60,466 cases and 53,461 controls. N. Engl. J. Med., in press."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1158\/0008-5472.CAN-19-0728","article-title":"Penetrance of different cancer types in families with Li-Fraumeni syndrome: A validation study using multi-center cohorts","volume":"80","author":"Shin","year":"2020","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1038\/bjc.1997.205","article-title":"Screening for TP53 mutations in patients and tumours from 109 Swedish breast cancer families","volume":"75","author":"Claro","year":"1997","journal-title":"Br. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10549-012-2375-z","article-title":"Prevalence of germline TP53 mutations in HER2+ breast cancer patients","volume":"139","author":"Rath","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hyder, Z., Harkness, E.F., Woodward, E.R., Bowers, N.L., Pereira, M., Wallace, A.J., Howell, S.J., Howell, A., Lalloo, F., and Newman, W.G. (2020). Risk of Contralateral Breast Cancer in Women with and without Pathogenic Variants in BRCA1, BRCA2, and TP53 Genes in Women with Very Early-Onset (<36 Years) Breast Cancer. Cancers, 12.","DOI":"10.3390\/cancers12020378"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/jmg.2004.030551","article-title":"Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation","volume":"43","author":"Figueiredo","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.canlet.2005.12.039","article-title":"The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families","volume":"245","author":"Achatz","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.canlet.2007.10.044","article-title":"Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil","volume":"261","author":"Palmero","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1590\/1678-4685-gmb-2014-0343","article-title":"Early-onset breast cancer patients in the South and Southeast of Brazil should be tested for the TP53 p.R337H mutation","volume":"39","author":"Andrade","year":"2016","journal-title":"Genet. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1093\/hmg\/ddx106","article-title":"Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage","volume":"26","author":"Zerdoumi","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/humu.23656","article-title":"Current review of TP53 pathogenic germline variants in breast cancer patients outside Li-Fraumeni syndrome","volume":"39","author":"Fortuno","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10689-018-00118-0","article-title":"TP53 germline mutation testing in early-onset breast cancer: Findings from a nationwide cohort","volume":"18","author":"Bakhuizen","year":"2019","journal-title":"Fam. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/cncr.26377","article-title":"Early onset HER2-positive breast cancer is associated with germline TP53 mutations","volume":"118","author":"Bojadzieva","year":"2012","journal-title":"Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/jnci\/djy001","article-title":"Differences in TP53 Mutation Carrier Phenotypes Emerge From Panel-Based Testing","volume":"110","author":"Rana","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1136\/jmg.2010.078113","article-title":"A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations","volume":"47","author":"Wilson","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s10549-012-1993-9","article-title":"Breast cancer phenotype in women with TP53 germline mutations: A Li-Fraumeni syndrome consortium effort","volume":"133","author":"Masciari","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kuba, M.G., Lester, S.C., Bowman, T., Stokes, S.M., Taneja, K.L., Garber, J.E., and Dillon, D.A. (2020). Histopathologic features of breast cancer in Li-Fraumeni syndrome. Mod. Pathol., Online ahead of print.","DOI":"10.1038\/s41379-020-0610-4"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/humu.24060","article-title":"Suggested application of HER2+ breast tumor phenotype for germline TP53 variant classification within ACMG\/AMP guidelines","volume":"41","author":"Fortuno","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.1038\/sj.onc.1204621","article-title":"Relative frequency and morphology of cancers in carriers of germline TP53 mutations","volume":"20","author":"Birch","year":"2001","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00428-013-1439-8","article-title":"A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil","volume":"463","author":"Giacomazzi","year":"2013","journal-title":"Virchows Arch."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1245\/s10434-020-08480-z","article-title":"Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing","volume":"27","author":"Rosenberger","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ejca.2018.06.011","article-title":"Contribution of genotoxic anticancer treatments to the development of multiple primary tumours in the context of germline TP53 mutations","volume":"101","author":"Kasper","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/S1470-2045(16)30249-2","article-title":"Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study","volume":"17","author":"Villani","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1158\/1078-0432.CCR-17-0408","article-title":"Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome","volume":"23","author":"Kratz","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hanson, H., Brady, A.F., Crawford, G., Eeles, R.A., Gibson, S., Jorgensen, M., Izatt, L., Sohaib, A., Tischkowitz, M., and Evans, D.G. (2020). UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants. J. Med. Genet.","DOI":"10.1136\/jmedgenet-2020-106876"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1001\/jamaoncol.2017.1968","article-title":"Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis","volume":"3","author":"Ballinger","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1001\/jamaoncol.2017.1358","article-title":"Lung Adenocarcinoma as Part of the Li-Fraumeni Syndrome Spectrum: Preliminary Data of the LIFSCREEN Randomized Clinical Trial","volume":"3","author":"Caron","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1001\/jamaoncol.2017.1346","article-title":"Surveillance of Dutch Patients with Li-Fraumeni Syndrome: The LiFe-Guard Study","volume":"3","author":"Ruijs","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s10689-017-9965-1","article-title":"Baseline results from the UK SIGNIFY study: A whole-body MRI screening study in TP53 mutation carriers and matched controls","volume":"16","author":"Saya","year":"2017","journal-title":"Fam. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10689-017-0034-6","article-title":"Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: Experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic","volume":"17","author":"Bojadzieva","year":"2018","journal-title":"Fam. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, A.F., Voss, S.D., Jagannathan, J.P., Kamihara, J., Nibecker, C., Itriago-Araujo, E., Masciari, S., Parker, E., Barreto, M., and London, W.B. (2018). Screening with whole-body magnetic resonance imaging in pediatric subjects with Li-Fraumeni syndrome: A single institution pilot study. Pediatr. Blood Cancer, 65.","DOI":"10.1002\/pbc.26822"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40644-018-0162-8","article-title":"Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: Observations from a two rounds screening of Brazilian patients","volume":"18","author":"Paixao","year":"2018","journal-title":"Cancer Imaging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1200\/JCO.2009.27.2112","article-title":"Genetic testing in Li-Fraumeni syndrome: Uptake and psychosocial consequences","volume":"28","author":"Lammens","year":"2010","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/12\/3762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:44:51Z","timestamp":1760179491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/12\/3762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,14]]},"references-count":69,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["cancers12123762"],"URL":"https:\/\/doi.org\/10.3390\/cancers12123762","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,14]]}}}