Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas
Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas
复制标题
DOI：
10.1016/j.jdermsci.2013.09.002
复制
发表时间：
2014-01-01
影响因子：
4.6
通讯作者：
Soares, Paula
中科院分区：
文献类型：
--
作者：
Boaventura, Paula;Pereira, Dina;Soares, Paula
背景：基底细胞癌（BCC）是最常见的皮肤癌。基底细胞癌的患病率升高与放射治疗有关，即在头皮炎脱毛治疗后，这些肿瘤被描述为更具侵袭性。线粒体DNA（mtDNA）突变已被报道在许多人类肿瘤，但它们的发生在BCC是不好documented.Objective：这项工作的目的是评估BCC的组织学亚型在个人进行X射线脱毛Taphthocapitis治疗相比，非照射患者。此外，我们还想评估线粒体D-Loop的不稳定性，在两组的基底细胞癌，以比较D-Loop突变的频率在照射后的基底细胞癌与散发性BCC.Methods：228个组织学标本相应的基底细胞癌从75例放疗患者和60例非放疗患者的组织学亚型进行了重新评估。随后，我们测序的D-环310重复在血液中，口腔粘膜，肿瘤病变，只要有，非肿瘤相邻组织从这些patients.Results：浸润型BCC亚型，被认为是更具侵略性，是显着更频繁的照射患者。照射组BCCD-Loop D310突变率显著高于对照组。此外，它与较高的辐射剂量有关。患者血液中mtDNA异质性的存在与BCCs中较高的突变率相关，这表明更不稳定的基因型可能易患mtDNA体细胞突变。结论：我们的研究结果表明，辐射诱导的BCCs可能被认为是更具侵略性的肿瘤。需要进一步的研究来阐明mtDNA D-Loop突变在辐射患者肿瘤中的作用。(C)2013年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented.Objective: The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC.Methods: 228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients.Results: The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation.Conclusions: Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.