title: Recommended Guidelines for Validation, Quality Control, and Reporting ofTP53Variants in Clinical Practice.
abstract: Accurate assessment ofTP53gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmedTP53as the most commonly mutated gene in human cancer. Analysis of a database of 70,000TP53variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrange-ments in intron 1 ofTP53are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessingTP53status in clinical samples. Finally, we discuss howTP53alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports.Cancer Res; 77(6); 1250-60. ©2017 AACR.
authors.affiliation: Sorbonne Université, UPMC Univ Paris 06, Paris, France.
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authors.affiliation: Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
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authors.affiliation: Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'H ematologie Biologique, France.
authors.forename: Fanny
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authors.affiliation: Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford, United Kingdom.
authors.forename: Gareth L
authors.initials: GL
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authors.affiliation: Dept of Pathology, School of Medicine, University of Otago, Dunedin, New Zealand.|Children's Medical Research Institute, University of Sydney, Westmead NSW, Australia.
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authors.affiliation: Department of Gynecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria.
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authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
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authors.affiliation: Department of Hematology/Oncology and Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
authors.affiliation: Service d'hématologie séniors, Hôpital St Louis/Université Paris 7, 1 avenue Claude Vellefaux, Paris, France.
authors.forename: Pierre
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authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Gianluca
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authors.lastname: Gaidano
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Anita
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authors.affiliation: Karolinska Institute, Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Hellstrom-Lindberg
authors.affiliation: Bergonié Cancer Institute University of Bordeaux 229 cours de l'Argonne 33076 Bordeaux, France.
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authors.affiliation: Molecular Oncology Unit, Hospital Saint Louis, Paris, France.
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authors.affiliation: Cancer Genetics Program, Magee Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
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authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
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authors.lastname: Malkin
authors.affiliation: Department of Pathology, Stony Brook University, Stony Brook, New York.
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authors.initials: UM
authors.lastname: Moll
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
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authors.affiliation: Department of Oncology, Division of Cancer Predisposition, St. Jude Children's Research Hospital, Memphis, Tennessee.
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authors.initials: KE
authors.lastname: Nichols
authors.affiliation: Masaryk University, CEITEC - Molecular Medicine and University Hospital Brno, Department of Internal Medicine - Hematology and Oncology, Brno, Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.affiliation: Universidade Federal do Rio Grande do Sul (UFRGS) e Serviço deGenética Médica-HCPA, Rua Ramiro Barcelos, Porto Alegre, Brasil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
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authors.initials: SA
authors.lastname: Savage
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Louise C
authors.initials: LC
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authors.affiliation: Departments of Medicine and Human Genetics, McGill University and Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
authors.affiliation: Molecular Oncology Group, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
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authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Joseph F
authors.initials: JF
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authors.affiliation: Generade Centre of Expertise Genomics and University of Applied Sciences Leiden, Leiden, the Netherlands.
authors.forename: Peter E M
authors.initials: PE
authors.lastname: Taschner
authors.affiliation: Institut Albert Bonniot, Inserm 823, Université Grenoble Alpes, Rond Point de la Chantourne, La Tronche, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.affiliation: Sorbonne Université, UPMC Univ Paris 06, Paris, France. thierry.soussi@ki.se thierry.soussi@upmc.fr.|Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.|INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Thierry
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authors.lastname: Soussi
mesh_terms: D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D017410:Practice Guidelines as Topic / Q000592:standards*; D011786:Quality Control; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D054928:Validation Studies as Topic
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53