TP53 Variations In Human Cancers: New Lessons From The IARC TP53 Database And Genomics Data

Magali OLIVIER, International Agency for Research on Cancer, France
BOUAOUN L. 2 , SONKIN D. 3 , ARDIN M. 1 , HOLLSTEIN M. 1,4 , BYRNES G. 2 , ZAVADIL J. 1

1 Molecular Mechanisms and Biomarkers Group, International Agency for Research on Cancer, Lyon, France
2 Biostatistics Group, International Agency for Research on Cancer, Lyon, France
3 Division of Cancer Treatment and Diagnosis, Biometric Research Program, National Cancer Institute, Rockville, USA
4 Faculty of Medicine and Health, University of Leeds, UK

Purpose
Mutations in the TP53 gene are among the most frequent somatic events in cancer. The IARC TP53 database (http://p53.iarc.fr/) compiles occurrence and phenotype data on TP53 germline and somatic variations linked to human cancer. The database is a popular resource appreciated for the quality and scope of its data and actively used worldwide. The deluge of data from cancer genomic studies generates new data on TP53 variations and attracts a growing number of database users for the interpretation of TP53 variants. Here, we present the current contents and functionalities of the IARC TP53 database and perform a systematic analysis of data extracted from the IARC database and from genomic data repositories.

Methods
Mutation frequency data were extracted from the IARC TP53 database (Sanger sequencing studies) and from TCGA and ICGC data portals (next generation sequencing - NGS - studies). Mutation distributions by protein location and by cancer types were computed and plotted using R software.    

Results
The IARC TP53 Database provides a broad scope of data on TP53 gene variations that can be queried with an advanced search interface. The available data on somatic mutations are more extensive than what is currently available in the genomic repositories, with larger number of TP53 mutations and more cancer types covered. However, the higher sensitivity and more complete screening achieved by NGS highlighted some overlooked facts about TP53 mutations, such as the presence of a significant number of mutations occurring outside the DNA-binding domain in certain cancer types. We also provide a list of variants that should be considered as neutral frequent variations and a list of cell-lines with their updated TP53 status.

Conclusions
The data presented will help users to efficiently use this resource and will provide an update of current knowledge on TP53 variations in human cancer.   

Funding sources
IARC