Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors

Abstract

Remarkably little is known about the transcriptional profiles of human embryonic stem (ES) cells or the molecular mechanisms that underlie their pluripotency. To identify commonalties among the transcriptional profiles of different human pluripotent cells and to search for clues into the genesis of human germ cell tumors, we compared the expression profiles of human ES cell lines, human germ cell tumor cell lines and tumor samples, somatic cell lines, and testicular tissue samples by using cDNA microarray analysis. Hierarchical cluster analysis of gene expression profiles showed that the five independent human ES cell lines clustered tightly together, reflecting highly similar expression profiles. The gene expression patterns of human ES cell lines showed many similarities with the human embryonal carcinoma cell samples and more distantly with the seminoma samples. We identified 895 genes that were expressed at significantly greater levels in human ES and embryonal carcinoma cell lines than in control samples. These genes are candidates for involvement in the maintenance of a pluripotent, undifferentiated phenotype.

Genomic copy number and expression patterns in testicular germ cell tumours

“…Tumour protein D52 isoform 2 (TPD52) encoded by a gene at 8q21.1 is described as the target for amplification of this region in breast and ovarian cancers (Balleine et al, 2000;Byrne et al, 2005). Mining of published expression microarray data for TGCTs (Sperger et al, 2003) revealed increased expression of TPD52 in TGCT compared to normal testis with an average fold increase of 3.2 and represents a good candidate for involvement in TGCT. Other differentially expressed genes in regions of imbalance were identified including cell division cycle associated 7 (CDCA7) localised to 2q31, which had an average 4.9-fold increase in expression compared with normal testis.…”

Origin of pluripotent germ cell tumours: The role of microenvironment during embryonic development

“…The phenotype of seminoma is very close to that of CIS, whereas the phenotype of EC, considered the undifferentiated stem cell compartment of nonseminomas, resembles much closer that of ES cells, suggesting a re-programming or a dedifferentiation event (Sperger et al, 2003;Almstrup et al, 2005;Skotheim et al, 2005;Korkola et al, 2006). This is supported by the high expression of SOX2 in EC (Perrett et al in press), for example, while in seminoma this marker is virtually negative (Sperger et al, 2003;Santagata et al, 2007).…”

“…The phenotype of seminoma is very close to that of CIS, whereas the phenotype of EC, considered the undifferentiated stem cell compartment of nonseminomas, resembles much closer that of ES cells, suggesting a re-programming or a dedifferentiation event (Sperger et al, 2003;Almstrup et al, 2005;Skotheim et al, 2005;Korkola et al, 2006). This is supported by the high expression of SOX2 in EC (Perrett et al in press), for example, while in seminoma this marker is virtually negative (Sperger et al, 2003;Santagata et al, 2007). A further somatic differentiation of EC is observed in nearly all nonseminomas and this event is associated with down-regulation/inactivation of the embryonic pluripotency genes ( CIS cells are known to undergo polyploidization and DNA content in the triploid to hypotetraploid range has been identified in CIS adjacent to both seminoma and non-seminoma (Ottesen et al, 2004b).…”

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

“…Several studies have focused on genes on chromosomes 17 and 12, because of frequent rearrangements of these chromosomes Rodriguez et al, 2003;. One study reported gene expression patterns of testicular SEM compared to normal testicular parenchyma (Okada et al, 2003), and another study have reported gene expression in SEM-and embryonic carcinoma (EC)-derived cell lines (Sperger et al, 2003). Our investigations have so far focussed on the preinvasive CIS stage of TGCTs, and we have recently reported the genome-wide gene expression profile of CIS (Almstrup et al, 2004;Hoei-Hansen et al, 2004a).…”