Horny Kai, Gerhardt Patricia, Hebel-Cherouny Angela, Wülbeck Corinna, Utikal Jochen, Becker Jürgen C
Translational Skin Cancer Research, German Cancer Consortium (DKTK), 45141 Essen, Germany.
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Cancers (Basel). 2021 Feb 5;13(4):649. doi: 10.3390/cancers13040649.
Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. However, the genomic characteristics of MCC cell lines used as preclinical models are not well established. Thus, we analyzed the exomes of three virus-negative and six virus-positive MCC cell lines, all showing a classical neuroendocrine growth pattern. Virus-negative cell lines are characterized by a high tumor mutational burden (TMB), UV-light-induced DNA damage, functionally relevant coding mutations, e.g., in and , and large amounts of copy number variations (CNVs). In contrast, virus-positive cell lines have a low TMB with few coding mutations and lack prominent mutational signatures, but harbor characteristic CNVs. One of the virus-negative cell lines has a local amplification associated with high mRNA expression. In conclusion, virus-positive and -negative MCC cell lines with a neuroendocrine growth pattern resemble mutational features observed in MCC tissue samples, which strengthens their utility for functional studies.
默克尔细胞癌（MCC）是一种罕见的、侵袭性很强的皮肤恶性肿瘤，它要么与默克尔细胞多瘤病毒的整合有关，要么与长期紫外线暴露有关。这两种致癌类型反映在MCC肿瘤病变中呈现的特征性突变特征上。然而，用作临床前模型的MCC细胞系的基因组特征尚未完全明确。因此，我们分析了三个病毒阴性和六个病毒阳性的MCC细胞系的外显子组，所有细胞系均呈现典型的神经内分泌生长模式。病毒阴性细胞系的特征是肿瘤突变负担（TMB）高、紫外线诱导的DNA损伤、功能相关的编码突变，例如在[具体基因名称1]和[具体基因名称2]中，以及大量的拷贝数变异（CNV）。相比之下，病毒阳性细胞系的TMB低，编码突变少，缺乏显著的突变特征，但具有特征性的CNV。其中一个病毒阴性细胞系存在局部[具体基因名称3]扩增，与高[具体基因名称3]mRNA表达相关。总之，具有神经内分泌生长模式的病毒阳性和阴性MCC细胞系类似于在MCC组织样本中观察到的突变特征，这增强了它们在功能研究中的实用性。
