GRCh38 · COSMIC v92


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Whole genome and whole transcriptome genomic profiling of a metastatic eccrine porocarcinoma.
Paper ID
Thibodeau ML, Bonakdar M, Zhao E, Mungall KL, Reisle C, Zhang W, Bye MH, Thiessen N, Bleile D, Mungall AJ, Ma YP, Jones MR, Renouf DJ, Lim HJ, Yip S, Ng T, Ho C, Laskin J, Marra MA, Schrader KA and Jones SJM
1Department of Medical Genetics, University of British Columbia, C201-4500 Oak Street, Vancouver, BC V6H 3N1 Canada.
NPJ precision oncology, 2018;2(1):8
ISSN: 2397-768X
PMID: 29872726 (view at PubMed or Europe PMC)
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 <i>APC</i>, <i>PTEN</i> and <i>CDKN2A</i>, <i>CDKN2B</i> and <i>CDKN1A</i>. We identified a somatic hemizygous <i>CDKN2A</i> pathogenic splice site variant. De novo transcriptome assembly revealed abnormal splicing of <i>CDKN2A</i> p14<sup>ARF</sup> and p16<sup>INK4a</sup>. Elevated expression of oncogenes <i>EGFR</i> and <i>NOTCH1</i> 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 <i>CDKN2A</i> 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.
Paper Status