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  • Title: A study of mitochondrial DNA D-loop mutations and p53 status in nonmelanoma skin cancer.
    Author: Prior SL, Griffiths AP, Lewis PD.
    Journal: Br J Dermatol; 2009 Nov; 161(5):1067-71. PubMed ID: 19624548.
    Abstract:
    BACKGROUND: Mitochondrial DNA (mtDNA) displacement-loop (D-loop) mutations have previously demonstrated potential as smoking-induced biomarkers in oral squamous cell carcinoma (SCC). Additionally, they have been observed in SCC and basal cell carcinoma of nonmelanoma skin cancer (NMSC). However, they have not been examined in the SCC precursor lesions, Bowen disease or actinic keratosis. OBJECTIVES: Here, we present a novel study of mtDNA D-loop mutations in these two precursors, a rare keratoacanthoma and NMSC (all tumours not related to smoking). METHODS: We used a polymerase chain reaction and direct sequencing approach. Furthermore, as the tumour suppressor protein p53 has been reported as having a novel role in maintaining mitochondrial genetic stability, we assessed p53 status using immunohistochemistry, evaluating potential association with the presence of mtDNA mutations. RESULTS: Of 36 tumours, nine (25%) exhibited mutations in the D-loop. In total, 13 base substitutions were observed across all patients: seven (53.8%) were A : T to G : C; two (15.4%) were G : C to T : A; two (15.4%) were G : C to A : T and two (15.4%) were G : C to C : G. Four of the 13 (30.8%) base substitutions were observed at nucleotide 146. We observed abnormal p53 accumulation in over half of the samples analysed (55.5%), suggesting it to be a major part of the carcinogenic process of NMSC; however; there was no association between p53 positivity and the presence of mtDNA mutations (P = 0.47). CONCLUSIONS: It is unlikely that alteration in p53 status is a contributing factor to mtDNA mutagenesis.
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