CNV Hotspots in Testicular Seminoma Tissue and Seminal Plasma

SIMPLE SUMMARY: Testicular seminoma represents the most common type of testicular germ cell tumours, which are the most prevalent malignancies among the male population in reproductive age. Thus, it is crucial to find novel biomarkers for early detection and improve patient management. Copy number variation (CNV) is associated with various cancers including seminoma. Therefore, the current study aims to investigate CNV of specific genes and determine their potential as a possible seminoma biomarker. CNVs were investigated in genomic DNA from seminoma tissue, as well as in cell-free DNA (cfDNA) from seminal plasma as liquid biopsy. We detected increased CNVs in tissue samples, as well as in cfDNA from seminal plasma. According to obtained data, seminoma CNV hotspots are present and are reflected in seminal plasma. Although clinical value is yet to be determined, presented data emphasize a potential use of CNV as an SE biomarker. ABSTRACT: Seminoma (SE) is the most frequent type of testicular tumour, affecting predominantly young men. Early detection and diagnosis of SE could significantly improve life quality and reproductive health after diagnosis and treatment. Copy number variation (CNV) has already been associated with various cancers as well as SE. In this study, we selected four genes (MAGEC2, NANOG, RASSF1A, and KITLG) for CNV analysis in genomic DNA (gDNA), which are located on chromosomes susceptible to gains, and whose aberrant expression was already detected in SE. Furthermore, CNV was analysed in cell-free DNA (cfDNA) from seminal plasma. Analysis was performed by droplet digital polymerase chain reaction (ddPCR) on gDNA from SE and nonmalignant testicular tissue. Seminal plasma cfDNA from SE patients before and after surgery was analysed, as well as from healthy volunteers. The CNV hotspot in gDNA from SE tissue was detected for the first time in all analysed genes, and for two genes, NANOG and KITLG it was reflected in cfDNA from seminal plasma. Although clinical value is yet to be determined, presented data emphasize a potential use of CNV as a potential SE biomarker from a liquid biopsy.