TY - JOUR
T1 - Recommended guidelines for validation, quality control, and reporting of TP53 variants in clinical practice
AU - Leroy, Bernard
AU - Ballinger, Mandy L.
AU - Baran-Marszak, Fanny
AU - Bond, Gareth L.
AU - Braithwaite, Antony
AU - Concin, Nicole
AU - Donehower, Lawrence A.
AU - El-Deiry, Wafik S.
AU - Fenaux, Pierre
AU - Gaidano, Gianluca
AU - Langerød, Anita
AU - Hellstrom-Lindberg, Eva
AU - Iggo, Richard
AU - Lehmann-Che, Jacqueline
AU - Mai, Phuong L.
AU - Malkin, David
AU - Moll, Ute M.
AU - Myers, Jeffrey N.
AU - Nichols, Kim E.
AU - Pospisilova, Sarka
AU - Ashton-Prolla, Patricia
AU - Rossi, Davide
AU - Savage, Sharon A.
AU - Strong, Louise C.
AU - Tonin, Patricia N.
AU - Zeillinger, Robert
AU - Zenz, Thorsten
AU - Fraumeni, Joseph F.
AU - Taschner, Peter E.M.
AU - Hainaut, Pierre
AU - Soussi, Thierry
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/3/15
Y1 - 2017/3/15
N2 - 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 9b and 9g, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrangements 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.
AB - 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 9b and 9g, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrangements 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.
UR - https://www.scopus.com/pages/publications/85015913590
U2 - 10.1158/0008-5472.CAN-16-2179
DO - 10.1158/0008-5472.CAN-16-2179
M3 - Review article
C2 - 28254861
AN - SCOPUS:85015913590
SN - 0008-5472
VL - 77
SP - 1250
EP - 1260
JO - Cancer Research
JF - Cancer Research
IS - 6
ER -