Eccrine porocarcinomas (EPs) are rare malignant tumours of the intraepidermic sweat gland duct and most often arise from benign eccrine poromas. Some recurrent somatic genomic events have been identified in these malignancies, but very little is known about the complexity of their molecular pathophysiology. We describe the whole genome and whole transcriptome genomic profiling of a metastatic EP in a 66-year-old male patient with a previous history of localized porocarcinoma of the scalp. Whole genome and whole transcriptome genomic profiling was performed on the metastatic EP. Whole genome sequencing was performed on blood-derived DNA in order to allow a comparison between germline and somatic events. We found somatic copy losses of several tumour suppressor genes including APC, PTEN and CDKN2A, CDKN2B and CDKN1A. We identified a somatic hemizygous CDKN2A pathogenic splice site variant. De novo transcriptome assembly revealed abnormal splicing of CDKN2A p14^ARF and p16^INK4a. Elevated expression of oncogenes EGFR and NOTCH1 was noted and no somatic mutations were found in these genes. Wnt pathway somatic alterations were also observed. In conclusion, our results suggest that the molecular pathophysiology of malignant EP features high complexity and subtle interactions of multiple key genes. Cell cycle dysregulation and CDKN2A loss of function was found to be a new potential driver in EP tumourigenesis. Moreover, the combination of somatic copy number variants and abnormal gene expression perhaps partly related to epigenetic mechanisms, all likely contribute to the development of this rare malignancy in our patient.

小汗腺孔癌（EP）是表皮内汗腺管的罕见恶性肿瘤，最常见于良性小汗腺孔瘤。在这些恶性肿瘤中已经发现了一些复发性体细胞基因组事件，但对其分子病理生理学的复杂性知之甚少。我们描述了一名 66 岁男性患者的转移性 EP 的全基因组和全转录组基因组分析，该患者既往有头皮局限性毛孔癌病史。对转移性 EP 进行全基因组和全转录组基因组分析。对血液来源的 DNA 进行全基因组测序，以便比较种系事件和体细胞事件。我们发现一些肿瘤抑制基因的体细胞拷贝丢失，包括APC 、 PTEN和CDKN2A 、 CDKN2B和CDKN1A 。我们鉴定了体细胞半合子CDKN2A致病性剪接位点变异。从头转录组组装揭示了CDKN2A p14 ^ARF和 p16 ^INK4a的剪接异常。注意到癌基因EGFR和NOTCH1的表达升高，并且在这些基因中未发现体细胞突变。还观察到 Wnt 通路体细胞改变。总之，我们的结果表明恶性 EP 的分子病理生理学具有高度复杂性和多个关键基因之间微妙的相互作用。细胞周期失调和CDKN2A功能丧失被发现是 EP 肿瘤发生的新潜在驱动因素。 此外，体细胞拷贝数变异和异常基因表达的组合可能部分与表观遗传机制有关，所有这些都可能导致我们患者发生这种罕见的恶性肿瘤。