The TP53 Database: transition from the International Agency for Research on Cancer to the US National Cancer Institute
2022; Springer Nature; Volume: 29; Issue: 5 Linguagem: Inglês
10.1038/s41418-022-00976-3
ISSN1476-5403
AutoresKelvin C. de Andrade, Elaine E. Lee, Elise M. Tookmanian, Chimene Kesserwan, James J. Manfredi, Jessica N. Hatton, Jennifer K. Loukissas, Jiří Zavadil, Lei Zhou, Magali Olivier, Megan N. Frone, Owais Shahzada, William J.R. Longabaugh, Christian P. Kratz, David Malkin, Pierre Hainaut, Sharon A. Savage,
Tópico(s)Molecular Biology Techniques and Applications
ResumoFrom 1994 through 2021, The International Agency for Research on Cancer (IARC) and the World Health Organization maintained a comprehensive database on variations in the tumor protein p53 gene (TP53), one of the most frequently mutated genes in human cancer.TP53 plays crucial roles in cell signaling, apoptosis, metabolism, DNA repair and transcription, earning it the moniker "guardian of the genome" (reviewed in [1]).Germline genetic variants in TP53 are the primary cause of Li-Fraumeni syndrome (LFS, OMIM 151623), a hereditary cancer predisposition disorder [2] associated with an approximately 24 times higher lifetime incidence of any cancer compared with the general population [3].The database was initiated by Hollstein et al. [4] and, posteriorly, developed and curated at IARC by Pierre Hainaut and Magali Olivier from 1995 until 2021.During this period, the dataset grew from 2500 to over 50,000 annotated variations in the current database release [5], making it the largest single-locus cancer database.The database has served as an important resource for numerous TP53-and LFS-associated studies.Since 1997, the key publications describing and referencing the database have accumulated over 9000 citations in the scientific and medical literature (source: Google Scholar; selected significant papers include [5][6][7][8]).Data from the IARC TP53 database have been widely mined and analyzed to systematically explore functional and structural properties of p53 variants [9][10][11], genotype-phenotype associations [12], temporal patterns of cancer penetrance [13], carcinogen-induced mutation signatures [14-16], and cancer prognosis and outcomes [17].The most recent publication using this database, as of the writing of this commentary, focused on the germline dataset and investigated differences in variant distribution and cancer patterns to better refine the variable LFS-associated phenotypic spectrum [18].On October 25th, 2021, the IARC-sponsored TP53 database was fully transferred to the US National Cancer Institute (NCI) to host and facilitate important upgrades to its infrastructure (https://tp53.isb-cgc.org).The original TP53 Database was run on an on-premises server at IARC, using a Microsoft platform.The NCI-sponsored TP53 Database is hosted on the Google Cloud Platform, primarily using its App Engine,
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