Poster Presentation ASPCR-ASDR Conference 2013

G to c polymorphism of p53 in codon 72 is common in actinic keratosis lesions (#116)

Miko Yamada 1 , Lynlee L Lin 1 , Kostantin Shakhbazov 2 , Marcel Dinger 2 , Elizabeth Payne 1 , Ian H Frazer 2 , Peter Soyer 1 , Tarl Prow 1
  1. Dermatology Research Centre, School of Medicine, University of Queensland, Translational Research Institute, Princess Alexandra Hospital, QLD, Australia
  2. Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane , QLD, Australia

Actinic Keratosis (AK) is a very common precancerous lesion in photoaged caucasians. AK can progress to squamous cell-carcinoma, but the factors leading to transformation are debatable with the tumour suppressor gene p53 being a recognised candidate. When p53 is up-regulated, it promotes either growth arrest or apoptosis in response to cellular injury as well as is critical for genomic stability maintenance. UV exposure is a known cause of p53 mutations. There is a highly conserved and crucial p53 domain for signalling apoptosis located between codons 64 and 92. Particularly, codon 72 variant is most common coding-region polymorphism of TP53 gene.
We collected 25 clincially diagnosed AK lesions by shave biopsy. Half of the lesion was subjected to histopathology and the other half processed for whole transcriptome sequencing. All lesions were hitopathologically diagnosed within the AK to squamous cell carcinoma progression lineage, except for one that was diagnosed as solar elastosis. Whole transcriptome sequencing data was placed for p53 mutation profiles. We found that these lesions contained p53 mRNA with a wide variety of polymorphisms. Only one polymorphism was present at a high frequency in all but one patient, G to C mutation in codon 72 of p53.
The results have indicated that G/C polymorphism of p53 in codon72 is common in samples from AK patients. This may play a role in skin cancer risk, its progression and the efficacy of therapy. Finally, we are investigating the use of this polymorphism as a biomarker for squamous cell carcinoma.