Oncogenomic Approaches in Exploring Gain of Function of Mutant p53
Pp. 143-160 (18)
Sara Donzelli, Francesca Biagioni, Francesca Fausti, Sabrina Strano, Giulia Fontemaggi and Giovanni Blandino
Cancer is caused by the spatial and temporal accumulation of alterations in
the genome of a given cell. This leads to the deregulation of key signaling pathways that
play a pivotal role in the control of cell proliferation and cell fate. The p53 tumor
suppressor gene is the most frequent target in genetic alterations in human cancers. The
primary selective advantage of such mutations is the elimination of cellular wild type
p53 activity. In addition, many evidences in vitro and in vivo have demonstrated that at
least certain mutant forms of p53 may possess a gain of function, whereby they
contribute positively to cancer progression. The fine mapping and deciphering of
specific cancer phenotypes is taking advantage of molecular-profiling studies based on
genome-wide approaches. Currently, high-throughput methods such as array-based
comparative genomic hybridization (CGH array), single nucleotide polymorphism array
(SNP array), expression arrays and ChIP-on-chip arrays are available to study mutant
p53-associated alterations in human cancers. Here we will mainly focus on the
integration of the results raised through oncogenomic platforms that aim to shed light
on the molecular mechanisms underlying mutant p53 gain of function activities and to
provide useful information on the molecular stratification of tumor patients.
CGH arrays, ChIP-chip, gain of function, mutant p53, oncogenomic
approaches, SNP arrays.
Translational Oncogenomics Unit, Regina Elena Cancer Institute, via Elio Chianesi, 53, 00144-Rome, Italy.