Genomic copy number and expression patterns in testicular germ cell tumours

Abstract

Testicular germ cell tumours of adults and adolescents (TGCT) include seminomas (SE) and nonseminomas (NS), with spermatocytic seminomas (SSE) representing a distinct entity in older men. SE and NS have gain of 12p material in all cases, whereas SSE are associated with overrepresentation of chromosome 9. Here, we compare at the chromosomal level, copy number imbalances with global expression changes, identified by comparative expressed sequence hybridisation analyses, in seven SE, one combined tumour, seven NS and seven cell lines. Positive correlations were found consistent with copy number as a main driver of expression change, despite reported differences in methylation status in SE and NS. Analysis of chromosomal copy number and expression data could not distinguish between SE and NS, in-keeping with a similar genetic pathogenesis. However, increased expression from 4q22, 5q23.2 and 9p21 distinguished SSE from SE and NS and decreased copy number and expression from 2q36 -q37 and 6q24 was a specific feature of NS-derived cell lines. Our analysis also highlights 19 regions with both copy number and expression imbalances in greater than 40% of cases. Mining available expression array data identified genes from these regions as candidates for involvement in TGCT development. Supplementary data is available at

Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors

“…S2). In addition to gain of 12p in individual samples, SCNAs were consistent with available historical data (van Echten et al 1995;Faulkner et al 2000;Looijenga et al 2000;Skotheim and Lothe 2003;McIntyre et al 2007;Litchfield et al 2015), notably recurrent pan-TGCT gains of Chromosomes 7, 8, 22, and X, and losses of Chromosomes 4,5,10,11,13,18, and Y (Fig. 1); also evident are the relative gains of Chromosomes 19 and 22 in SEs relative to NSEs (van Echten et al 1995;Summersgill et al 1998).…”

Overexpressed oncogenic tumor-self antigens

“…TPD52 overexpression has been demonstrated in several human malignancies including breast, [76][77][78] prostate, [79][80][81] and ovarian carcinomas. 82 Expression microarray and other analyses predict TPD52 overexpression in many other cancers including multiple myeloma, 83,84 Burkitt's lymphoma, 85,86 pancreatic cancer, 87 testicular germ cell tumors, [88][89][90] and melanomas, 91,92 as well as multiple other adult and pediatric cancers. 93 Murine ortholog of TPD52 The murine ortholog of TPD52 (mD52) parallels normal tissue expression patterns and known functions of human TPD52 (hD52), with 86% amino acid identity.…”

Genetic aspects of testicular germ cell tumors

“…1,6,55,56 Overall, the data suggest a close correlation between the two, in which the expression drives the chromosomal imbalances or vice versa.…”