Developing a mitochondrial DNA platform for predictive skin cancer bio-markers
Supervisor: Dr James Murphy
Funding: Irish Research Council
Non-melanoma skin cancer is the most common form of cancer diagnosed in Ireland, with numbers increasing yearly. It is most commonly caused by exposure to UV light, which promotes carcinogenesis through alterations in DNA. Nuclear DNA damage is removed either through repair or apoptosis, but mitochondrial DNA (mtDNA) damage persists and indeed accumulates throughout an individual’s life, serving as a molecular fingerprint of an individual’s sun exposure history as well as possessing potential as a predictive biomarker platform since heterogeneous mtDNA populations exist in the cell without causing loss of function, unless a majority of mtDNA carries the same mutation or deletion.
Total DNA including mtDNA was isolated from human skin biopsies taken from sun-exposed and non-exposed sites, including in some cases histologically normal skin near a non-melanoma skin cancer. Specific mtDNA deletions and mutations were evaluated using conventional and real time Polymerase Chain Reaction (PCR). Long range PCR was also employed as a method of measuring global mitochondrial genome damage and identifying further deletion events.
Some mtDNA damage accumulation appears to be proportional with cumulative sun exposure and varies greatly between individuals. Some mtDNA damage accumulation appears to be proportional with chronologic ageing.
Specific mtDNA damage events appear to accumulate with either ageing or cumulative sunlight exposure. Future work will evaluate whether and to what extent damage events and changes in gene expression can also be linked to cancerous skin such that a mitochondrial diagnostics platform for skin cancer biomarkers can be developed.