Genetic features of cancer of unknown primary

Background. Cancer of unknown primary (CUP) is a metastatic lesion with difficult identification of the primary tumor site using standard diagnostic approaches. Although the incidence of CUP is not high, this type of cancer often shows a high aggressiveness and therapy resistance and results in poor patient survival. The mechanisms of CUP origin are not clear, and further studies are needed. This study aims to analyze the mutational landscape of CUP and identify specific genetic alterations. Material and Methods. Whole exome sequencing was used to analyze the mutational landscape of CUP. Results. CUP had single nucleotide variants (SNVs) in the EPHA8 (ephrin receptor) gene. CUP also harbored copy number variations (CNAs) in the ID2, FOXD4, ZMYND11, ZNF596, KIDINS220, LRRN1, GEMIN4, CEP72, TPPP, and MXRA5 genes. According to functional enrichment analysis, these genes are involved in the regulation of transcription, biogenesis of microRNA, cellular cytoskeleton, adhesion, extracellular matrix remodeling, proliferation, apoptosis, and epithelial-mesenchymal transition. Conclusion. Cancer of unknown primary harbors mutations in the genes that regulate different biological processes particularly cell motility.