Mühleisen Beda, Petrov Ivaylo, Frigerio Simona, Dziunycz Piotr, French Lars E, Hofbauer Günther F L
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Arch Dermatol. 2012 Jun;148(6):697-703. doi: 10.1001/archdermatol.2012.107.
To evaluate chromosomal instability at 9p21-22 with p16 protein expression in organ transplant recipients (OTRs) compared with immunocompetent patients with squamous cell carcinoma (SCC).
In a select population of intraepithelial and subsequent invasive SCC from the same anatomic region of the same patient at different times, we assessed loss of heterozygosity at 3 microsatellites—IFNA, D9S162, and D9S925—in the course of carcinogenesis in OTRs and immunocompetent patients.
Department of Dermatology, University Hospital Zurich.
Immunocompetent patients and OTRs with SCC on sun-damaged skin.
Chromosomal allelic balance in SCC of OTRs and immunocompetent patients.
Reduced allelic balance at IFNA, D9S162, and D9S925 in intraepithelial forms of SCC and similar allelic imbalance in invasive forms of SCC were found. Allelic balance at D9S162 was reduced for SCC in OTRs compared with SCC in immunocompetent patients. The study revealed broadly reduced allelic balance at 9p21-22 in all cutaneous SCCs, and OTRs presented a further reduced allelic balance for D9S162, suggesting a common trait for SCC in OTRs. Actinic keratosis and Bowen disease differed in allelic balance at D9S162, suggesting substantial differences in their carcinogenesis.
Reduced allelic balance around locus D9S162 is a genomic correlate for enhanced carcinogenesis in OTRs.
评估器官移植受者(OTR)中9p21 - 22处的染色体不稳定性及p16蛋白表达,并与免疫功能正常的鳞状细胞癌(SCC)患者进行比较。
在同一患者不同时间来自相同解剖区域的上皮内及随后的浸润性SCC的特定人群中,我们评估了OTR和免疫功能正常患者在致癌过程中3个微卫星(IFNA、D9S162和D9S925)的杂合性缺失情况。
苏黎世大学医院皮肤科。
免疫功能正常的患者以及皮肤受阳光损伤且患有SCC的OTR。
OTR和免疫功能正常患者SCC中的染色体等位基因平衡。
发现SCC上皮内形式中IFNA、D9S162和D9S925的等位基因平衡降低,浸润性SCC中存在类似的等位基因失衡。与免疫功能正常患者的SCC相比,OTR中SCC的D9S162等位基因平衡降低。研究显示,所有皮肤SCC中9p21 - 22处的等位基因平衡普遍降低,OTR中D9S162的等位基因平衡进一步降低,提示OTR中SCC存在共同特征。光化性角化病和鲍温病在D9S162的等位基因平衡上存在差异,表明它们在致癌过程中有显著差异。
D9S162位点周围等位基因平衡降低是OTR中致癌作用增强的基因组相关因素。