Cancer is a result of a number of genetic alterations that disturb normal, controlled cell growth and differentiation. Mutational events leading to the activation of oncogenes or the inactivation of tumor-suppressor genes have been linked causally to the formation of tumors. p53 is one of the most important regulators of transcription, cellular cycle, DNA repair and apoptosis detected to date. Anti-p53 antibodies have been detected in the serum of cancer patients. This immune response is probably due to a self-immunization process linked to the strong immunogenicity of the p53 protein, and is associated predominantly with p53 missense mutation and p53 accumulation in the tumor. Auto-antibodies have also been proposed as potential diagnostic biomarkers for early stage diagnosis of cancers, since an increase in serum levels of certain auto-antibodies has been shown to precede the development of disease symptoms and correlate with cancer incidence for various cancers including breast and lung cancer.
Here we systematically evaluate reactivity of antibodies in p53 positive serum samples and identify reactive epitopes to normal and mutant peptides using a high-density (2.9 Million) peptide microarray. We assess the effect of linker length, peptide length, and flanking serines on antibody detection. We propose peptide array design parameters that can be applied to a whole proteome level to enable biomarker discovery and validation of novel auto-antibody epitopes associated with cancer.
Citation Format: Ken C. Lo, John C. Tan, Eric Sullivan, Ryan Bannen, Todd Richmond, Florian Grupp, Stefan Weiser, Dieter Heindl, Klaus-Peter Stengele, Albert Thomas. Anti-p53 auto-antibody serum profiling using high-density peptide arrays. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A156.
- ©2016 American Association for Cancer Research.