Abstract：
The most common type of melanoma is cutaneous melanoma (CM). The predominant mutational signature is that of ultraviolet radiation (UVR) exposure. The Cancer Genome Atlas (TCGA) molecular classification includes four major subtypes of CM based on common genetic alterations involving the following genes: BRAF, NRAS, and NF1, with a small fraction being \"triple\" wild-type. The two main signaling pathway abnormalities in CM are the mitogen-activated protein kinase (MAPK) pathway and the phosphoinositol-3-kinase (PI3K) pathway. Other less common types include mucosal melanomas (MM) and uveal melanoma (UM), which have a significantly different genomic landscape. Although few studies reported rare cases with HPV-positive (HPV+) melanoma, the clinicopathological and molecular characteristic of this entity has not been well-described. Among the 2084 melanoma cases queried at our institution, we identified seven patients diagnosed with HPV+ melanoma (prevalence 0.03 %), including five instances of CM and two of MM. The majority of cases were positive for HPV16 (n = 6). Most of the patients were elderly and with advanced disease (n = 6), although this finding may be attributed to the relative frequency of our institution testing advanced-stage tumors. Histologically, most cases showed high degree of pleomorphism and high mitotic count (5 or more mitoses/mm2) (n = 6). UVR signature was present in the CM, but not in the MM cases. Alterations in either MAPK and/or PI3K pathways were detected in the majority of cases (n = 6). The most common genetic abnormalities detected in this study occurred in the TERT promoter (TERTp) (n = 5), a finding that has been reported to be associated with aggressive disease. Our data shows that while HPV+ melanoma is rare, identifying this disease entity could help guide therapy given the demonstrated genomic alterations.
摘要：
最常见的黑素瘤类型是皮肤黑素瘤(CM)。主要的突变特征是紫外线辐射(UVR)暴露。癌症基因组图谱（TCGA）分子分类包括基于涉及以下基因的常见遗传改变的四种主要CM亚型：BRAF，NRAS,和NF1，一小部分是“三重”野生型。CM中的两个主要信号通路异常是丝裂原活化蛋白激酶(MAPK)通路和磷酸肌醇-3-激酶(PI3K)通路。其他不太常见的类型包括粘膜黑色素瘤（MM）和葡萄膜黑色素瘤（UM），它们具有明显不同的基因组景观。尽管很少有研究报道HPV阳性（HPV+）黑色素瘤的罕见病例，该实体的临床病理和分子特征尚未得到充分描述。在我们机构查询的2084例黑色素瘤病例中，我们确定了7例诊断为HPV+黑色素瘤的患者（患病率为0.03％），包括五个CM实例和两个MM实例。大多数病例为HPV16阳性（n=6）。大多数患者为老年人和晚期疾病（n=6），尽管这一发现可能归因于我们机构检测晚期肿瘤的相对频率。组织学上,大多数病例表现出高度的多态性和高的有丝分裂计数（5个或更多的有丝分裂/mm2）（n=6）。UVR签名存在于CM中，但不是在MM的情况下。在大多数情况下(n=6)检测到MAPK和/或PI3K途径的改变。在这项研究中检测到的最常见的遗传异常发生在TERT启动子（TERTp）（n=5），据报道，这一发现与侵袭性疾病有关。我们的数据显示，虽然HPV+黑色素瘤很少见，鉴于已证明的基因组改变，识别这种疾病实体可以帮助指导治疗。
