Hill Natasha T, Kim David, Busam Klaus J, Chu Emily Y, Green Clayton, Brownell Isaac
Dermatology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Marshfield Center, Marshfield, WI 02050, USA.
Cancers (Basel). 2021 Mar 6;13(5):1134. doi: 10.3390/cancers13051134.
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes and sequence mutations, little is known about genomic structural variants in MCC. To identify copy number variants in commonly altered genes, we analyzed genomic DNA from 31 tumor samples using the Nanostring nCounter copy number cancer panel. Unsupervised clustering revealed three tumor groups with distinct genomic structural variant signatures. The first cluster was characterized by multiple recurrent deletions in genes such as and . The second cluster contained eight VP-MCC and displayed very few structural variations. The final cluster contained one VP-MCC and four VN-MCC with predominantly genomic amplifications in genes like , , and and deletions in . Overall, VN-MCC contained more structure variation than VP-MCC but did not cluster separately from VP-MCC. The observation that most MCC tumors demonstrate a deletion-dominated structural group signature, independent of virus status, suggests a shared pathophysiology among most VP-MCC and VN-MCC tumors.
默克尔细胞癌（MCC）是一种罕见的侵袭性神经内分泌皮肤癌。大多数MCC肿瘤含有整合的默克尔细胞多瘤病毒DNA（病毒阳性MCC，VP-MCC），体细胞突变负担较低，而病毒阴性MCC（VN-MCC）则有许多紫外线特征性突变。与病毒癌基因和序列突变不同，关于MCC中的基因组结构变异知之甚少。为了鉴定常见改变基因中的拷贝数变异，我们使用纳米串nCounter拷贝数癌症检测板分析了31个肿瘤样本的基因组DNA。无监督聚类揭示了三个具有不同基因组结构变异特征的肿瘤组。第一组的特征是多个基因如 和 发生反复缺失。第二组包含8个VP-MCC，结构变异很少。最后一组包含1个VP-MCC和4个VN-MCC，主要在基因如 、 和 中发生基因组扩增，而 在 中发生缺失。总体而言，VN-MCC比VP-MCC含有更多的结构变异，但并未与VP-MCC分开聚类。大多数MCC肿瘤表现出以缺失为主的结构组特征，与病毒状态无关，这一观察结果表明大多数VP-MCC和VN-MCC肿瘤具有共同的病理生理学。
