School of Medicine, Institute of Life Science, Swansea University, Singleton Park, Swansea, UK.
Br J Dermatol. 2009 Nov;161(5):1067-71. doi: 10.1111/j.1365-2133.2009.09304.x. Epub 2009 May 11.
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.
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).
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.
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).
It is unlikely that alteration in p53 status is a contributing factor to mtDNA mutagenesis.
线粒体 DNA（mtDNA）的置换环（D-环）突变已被证明在口腔鳞状细胞癌（SCC）中具有作为吸烟诱导生物标志物的潜力。此外，它们还在 SCC 和非黑色素瘤皮肤癌（NMSC）的基底细胞癌中被观察到。然而，它们尚未在 SCC 前体病变、鲍文病或光化性角化病中进行检查。
本研究旨在探讨 D-环 mtDNA 突变在这两种前体病变（一种罕见的角化棘皮瘤和非吸烟相关的 NMSC）中的情况。
我们使用聚合酶链反应和直接测序方法。此外，由于肿瘤抑制蛋白 p53 已被报道在维持线粒体遗传稳定性方面具有新的作用，我们使用免疫组织化学评估了 p53 状态，评估了其与 mtDNA 突变存在的潜在关联。
在 36 个肿瘤中，有 9 个（25%）在 D-环中显示出突变。总共在所有患者中观察到 13 个碱基取代：7 个（53.8%）为 A：T 至 G：C；2 个（15.4%）为 G：C 至 T：A；2 个（15.4%）为 G：C 至 A：T 和 2 个（15.4%）为 G：C 至 C：G。在 13 个碱基取代中，有 4 个（30.8%）发生在核苷酸 146 处。我们观察到超过一半的分析样本中存在异常的 p53 积累（55.5%），这表明它是 NMSC 致癌过程的主要部分；然而，p53 阳性与 mtDNA 突变的存在之间没有关联（P=0.47）。
p53 状态的改变不太可能是 mtDNA 突变的促成因素。
