Helbig Doris, Quaas Alexander, Mauch Cornelia, Merkelbach-Bruse Sabine, Büttner Reinhard, Emberger Michael, Wobser Marion, Rüsseler Vanessa, Pütz Katharina, Binot Elke, Rehker Jan, Budczies Jan, Ihle Michaela Angelika
Department of Dermatology, University Hospital Cologne, Cologne, Germany.
Institute of Pathology, University Hospital Cologne, Cologne, Germany.
Oncotarget. 2017 Nov 25;8(65):109457-109467. doi: 10.18632/oncotarget.22691. eCollection 2017 Dec 12.
Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are frequent cutaneous sarcomas typically arising on sun-exposed skin in elderly patients. In contrast to AFX, which generally do not recur after complete excision, PDS locally recur in up to 50% and metastasize in up to 20%. We recently detected characteristic UV-induced mutations as potential driver mutation in almost all PDS investigated as well as activating and gene mutations in around one third of our tumors representing targets for personalized treatments in patients with unresectable or metastasized PDS. In the present study, we identified amplifications and deletions in a small part of the PDS (6 of 27 cases) but not in AFX suggesting that copy number variations (CNV) might not be an initial event in tumor development but rather important during tumor progression. In addition to and amplification, CNV analyses revealed deletions in the , and genes. In cases where an appropriate FISH assay was established, the CNV results could be verified by FISH analysis. Amplification of or and/or losses of might represent bad prognostic markers, although larger studies are needed to clarify their association with prognosis or progression in PDS.
非典型纤维黄色瘤（AFX）和多形性皮肤肉瘤（PDS）是常见的皮肤肉瘤，通常发生于老年患者暴露于阳光下的皮肤。与AFX不同，AFX完整切除后一般不复发，而PDS局部复发率高达50%，转移率高达20%。我们最近在几乎所有研究的PDS中检测到特征性紫外线诱导突变作为潜在驱动突变，并且在约三分之一的肿瘤中检测到激活和基因突变，这些突变代表了不可切除或转移性PDS患者个性化治疗的靶点。在本研究中，我们在一小部分PDS（27例中的6例）中发现了扩增和缺失，但在AFX中未发现，这表明拷贝数变异（CNV）可能不是肿瘤发生的初始事件，而是在肿瘤进展过程中起重要作用。除了和扩增外，CNV分析还揭示了、和基因的缺失。在建立了合适的荧光原位杂交（FISH）检测方法的病例中，CNV结果可通过FISH分析得到验证。或的扩增和/或的缺失可能代表不良预后标志物，尽管需要更大规模的研究来阐明它们与PDS预后或进展的关系。
