Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice
Bernard Leroy
(1)
,
Mandy L Ballinger
,
Fanny Baran-Marszak
(2)
,
Gareth L Bond
(3, 4, 5)
,
Antony Braithwaite
(6, 7)
,
Nicole Concin
(8)
,
Lawrence A Donehower
(9)
,
Wafik S. El-Deiry
(10)
,
Pierre P. Fenaux
(11)
,
Gianluca Gaidano
(12)
,
Anita Langerød
(13)
,
Eva Hellström-Lindberg
(14, 15)
,
Richard Iggo
(16, 17)
,
Jacqueline Lehmann-Che
(18)
,
Phuong L Mai
(19)
,
David Malkin
(20, 21)
,
Ute M. Moll
(22)
,
Jeffrey N Myers
(23)
,
Kim E Nichols
(24)
,
Sarka C Pospisilova
(25)
,
Patricia Ashton-Prolla
(26)
,
Davide Rossi
(12)
,
Sharon A Savage
,
Louise C Strong
(23)
,
Patricia N Tonin
(27)
,
Robert Zeillinger
(28)
,
Thorsten Zenz
(29)
,
Joseph F Fraumeni
(30)
,
Peter E.M. Taschner
(31)
,
Pierre Hainaut
(32, 33, 34, 35)
,
Thierry Soussi
(15, 36, 37)
1
SU -
Sorbonne Université
2 Hôpital Avicenne [AP-HP]
3 Ludwig Institute for Cancer Research
4 University of Oxford
5 Nuffield Department of Clinical Medicine [Oxford]
6 University of Otago [Dunedin, Nouvelle-Zélande]
7 The University of Sydney
8 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
9 BCM - Baylor College of Medicine
10 Fox Chase Cancer Center
11 Service d'hématologie clinique [Avicenne]
12 UPO - Università degli Studi del Piemonte Orientale - Amedeo Avogadro
13 Oslo University Hospital [Oslo]
14 Karolinska University Hospital [Stockholm]
15 Karolinska Institutet [Stockholm]
16 Institut Bergonié [Bordeaux]
17 UB - Université de Bordeaux
18 Hôpital Saint-Louis
19 University of Pittsburgh School of Medicine
20 SickKids - The Hospital for sick children [Toronto]
21 University of Toronto
22 SBU - Stony Brook University [SUNY]
23 The University of Texas M.D. Anderson Cancer Center [Houston]
24 St Jude Children's Research Hospital
25 MUNI - Masaryk University [Brno]
26 UFRGS - Universidade Federal do Rio Grande do Sul [Porto Alegre]
27 McGill University = Université McGill [Montréal, Canada]
28 University of Vienna [Vienna]
29 University of Heidelberg, Medical Faculty
30 NCI-NIH - National Cancer Institute [Bethesda]
31 Universiteit Leiden = Leiden University
32 IPRI - International Prevention Research Institute
33 Institut Albert Bonniot
34 UGA [2016-2019] - Université Grenoble Alpes [2016-2019]
35 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
36 CCK - Cancer Center Karolinska [Karolinska Institutet]
37 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
2 Hôpital Avicenne [AP-HP]
3 Ludwig Institute for Cancer Research
4 University of Oxford
5 Nuffield Department of Clinical Medicine [Oxford]
6 University of Otago [Dunedin, Nouvelle-Zélande]
7 The University of Sydney
8 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
9 BCM - Baylor College of Medicine
10 Fox Chase Cancer Center
11 Service d'hématologie clinique [Avicenne]
12 UPO - Università degli Studi del Piemonte Orientale - Amedeo Avogadro
13 Oslo University Hospital [Oslo]
14 Karolinska University Hospital [Stockholm]
15 Karolinska Institutet [Stockholm]
16 Institut Bergonié [Bordeaux]
17 UB - Université de Bordeaux
18 Hôpital Saint-Louis
19 University of Pittsburgh School of Medicine
20 SickKids - The Hospital for sick children [Toronto]
21 University of Toronto
22 SBU - Stony Brook University [SUNY]
23 The University of Texas M.D. Anderson Cancer Center [Houston]
24 St Jude Children's Research Hospital
25 MUNI - Masaryk University [Brno]
26 UFRGS - Universidade Federal do Rio Grande do Sul [Porto Alegre]
27 McGill University = Université McGill [Montréal, Canada]
28 University of Vienna [Vienna]
29 University of Heidelberg, Medical Faculty
30 NCI-NIH - National Cancer Institute [Bethesda]
31 Universiteit Leiden = Leiden University
32 IPRI - International Prevention Research Institute
33 Institut Albert Bonniot
34 UGA [2016-2019] - Université Grenoble Alpes [2016-2019]
35 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
36 CCK - Cancer Center Karolinska [Karolinska Institutet]
37 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
Mandy L Ballinger
- Fonction : Auteur
Fanny Baran-Marszak
- Fonction : Auteur
- PersonId : 1216303
- IdHAL : fanny-baran-marszak
- ORCID : 0000-0002-3723-2927
Gianluca Gaidano
- Fonction : Auteur
- PersonId : 885995
Jacqueline Lehmann-Che
- Fonction : Auteur
- PersonId : 762669
- ORCID : 0000-0001-6685-3354
David Malkin
- Fonction : Auteur
- PersonId : 758621
- ORCID : 0000-0001-5752-9763
Sharon A Savage
- Fonction : Auteur
Thierry Soussi
- Fonction : Auteur
- PersonId : 4907
- IdHAL : thierry-soussi
- ORCID : 0000-0001-8184-3293
- IdRef : 032043201
Résumé
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.