Accurate assessment of TP53 gene 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 confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants 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 of TP53 are 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 assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports. Cancer Res; 77(6); 1250-60. ©2017 AACR.

Bergonié Cancer Institute University of Bordeaux 229 cours de l'Argonne 33076 Bordeaux France

Cancer Division Garvan Institute of Medical Research Darlinghurst NSW Australia

Cancer Genetics Program Magee Womens Hospital University of Pittsburgh Medical Center Pittsburgh Pennsylvania

Children's Medical Research Institute University of Sydney Westmead NSW Australia

Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland

Department of Genetics Institute for Cancer Research Oslo University Hospital Oslo Norway

Department of Gynecology and Obstetrics Innsbruck Medical University Innsbruck Austria

Department of Hematology Oncology and Molecular Therapeutics Program Fox Chase Cancer Center Philadelphia Pennsylvania

Department of Oncology Division of Cancer Predisposition St Jude Children's Research Hospital Memphis Tennessee

Department of Oncology Pathology Karolinska Institutet Cancer Center Karolinska Stockholm Sweden

Department of Pathology Stony Brook University Stony Brook New York

Departments of Medicine and Human Genetics McGill University and Cancer Research Program The Research Institute of the McGill University Health Centre Montreal Quebec Canada

Dept of Pathology School of Medicine University of Otago Dunedin New Zealand

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland

Division of Hematology Department of Translational Medicine Amedeo Avogadro University of Eastern Piedmont Novara Italy

Division of Hematology Oncology Department of Pediatrics The Hospital for Sick Children University of Toronto Toronto Ontario Canada

Generade Centre of Expertise Genomics and University of Applied Sciences Leiden Leiden the Netherlands

Hôpital Avicenne Assistance Publique Hôpitaux De Paris Bobigny Service D'H ematologie Biologique France

Human Genome Sequencing Center Baylor College of Medicine Houston Texas

INSERM U1138 Centre de Recherche des Cordeliers Paris France

Institut Albert Bonniot Inserm 823 Université Grenoble Alpes Rond Point de la Chantourne La Tronche France

Karolinska Institute Department of Medicine Center for Hematology and Regenerative Medicine Karolinska University Hospital Stockholm Sweden

Ludwig Institute for Cancer Research University of Oxford Nuffield Department of Clinical Medicine Old Road Campus Research Building Oxford United Kingdom

Masaryk University CEITEC Molecular Medicine and University Hospital Brno Department of Internal Medicine Hematology and Oncology Brno Czech Republic

Molecular Oncology Group Department of Obstetrics and Gynaecology Medical University of Vienna Vienna Austria

Molecular Oncology Unit Hospital Saint Louis Paris France

Service d'hématologie séniors Hôpital St Louis Université Paris 7 1 avenue Claude Vellefaux Paris France

Sorbonne Université UPMC Univ Paris 06 Paris France

The University of Texas MD Anderson Cancer Center Houston Texas

Universidade Federal do Rio Grande do Sul e Serviço deGenética Médica HCPA Rua Ramiro Barcelos Porto Alegre Brasil

University of Heidelberg Department of Medicine 5 Heidelberg Germany; Department of Translational Oncology National Center for Tumor Diseases and German Cancer Research Center Heidelberg Germany

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Dysregulation of the p53 pathway provides a therapeutic target in aggressive pediatric sarcomas with stem-like traits

Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene

TP53 aberrations in chronic lymphocytic leukemia: an overview of the clinical implications of improved diagnostics

Germline mutation in the TP53 gene in uveal melanoma

ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation