Format

Send to

Choose Destination
Cancer Res. 2017 Mar 15;77(6):1250-1260. doi: 10.1158/0008-5472.CAN-16-2179.

Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice.

Author information

1
Sorbonne Université, UPMC Univ Paris 06, Paris, France.
2
Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
3
Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'H ematologie Biologique, France.
4
Ludwig Institute for Cancer Research, University of Oxford, Nuffield Department of Clinical Medicine, Old Road Campus Research Building, Oxford, United Kingdom.
5
Dept of Pathology, School of Medicine, University of Otago, Dunedin, New Zealand.
6
Children's Medical Research Institute, University of Sydney, Westmead NSW, Australia.
7
Department of Gynecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria.
8
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
9
Department of Hematology/Oncology and Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
10
Service d'hématologie séniors, Hôpital St Louis/Université Paris 7, 1 avenue Claude Vellefaux, Paris, France.
11
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
12
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
13
Karolinska Institute, Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden.
14
Bergonié Cancer Institute University of Bordeaux 229 cours de l'Argonne 33076 Bordeaux, France.
15
Molecular Oncology Unit, Hospital Saint Louis, Paris, France.
16
Cancer Genetics Program, Magee Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
17
Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
18
Department of Pathology, Stony Brook University, Stony Brook, New York.
19
The University of Texas MD Anderson Cancer Center, Houston, Texas.
20
Department of Oncology, Division of Cancer Predisposition, St. Jude Children's Research Hospital, Memphis, Tennessee.
21
Masaryk University, CEITEC - Molecular Medicine and University Hospital Brno, Department of Internal Medicine - Hematology and Oncology, Brno, Czech Republic.
22
Universidade Federal do Rio Grande do Sul (UFRGS) e Serviço deGenética Médica-HCPA, Rua Ramiro Barcelos, Porto Alegre, Brasil.
23
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
24
Departments of Medicine and Human Genetics, McGill University and Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
25
Molecular Oncology Group, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria.
26
University of Heidelberg, Department of Medicine V, Heidelberg, Germany; Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center (dkfz), Heidelberg, Germany.
27
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
28
Generade Centre of Expertise Genomics and University of Applied Sciences Leiden, Leiden, the Netherlands.
29
Institut Albert Bonniot, Inserm 823, Université Grenoble Alpes, Rond Point de la Chantourne, La Tronche, France.
30
Sorbonne Université, UPMC Univ Paris 06, Paris, France. thierry.soussi@ki.se thierry.soussi@upmc.fr.
31
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Stockholm, Sweden.
32
INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France.

Abstract

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.

PMID:
28254861
DOI:
10.1158/0008-5472.CAN-16-2179
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center