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

Leroy B1, Ballinger ML2, Baran-Marszak F3, Bond GL4, Braithwaite A5,6, Concin N7, Donehower LA8, El-Deiry WS9, Fenaux P10, Gaidano G11, Langerød A12, Hellstrom-Lindberg E13, Iggo R14, Lehmann-Che J15, Mai PL16, Malkin D17, Moll UM18, Myers JN19, Nichols KE20, Pospisilova S21, Ashton-Prolla P22, Rossi D11, Savage SA23, Strong LC19, Tonin PN24, Zeillinger R25, Zenz T26, Fraumeni JF Jr27, Taschner PE28, Hainaut P29, Soussi T30,31,32.

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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); 1-11. ©2017 AACR.