Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4

Abstract

Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in normal testes. Transcripts of maternally expressed 3 transcripts were expressed in seminoma without correlation with delta-like 1 homologue expression indicating an impaired imprinting status in seminoma. Interestingly, the transcripts of bromodomain-containing 2 and nuclear autoantigenic sperm protein associated with spermatogenesis were significantly upregulated in progressing tumour stages. Transcription factors TEA domain family member 4 and ETS variant gene 4 (ETV4), weakly expressed in normal testis, were strongly augmented during tumourigenesis. For ETV4 expression, a significant correlation with the increased expression of matrix metalloproteinase 2 and a disintegrin and metalloproteinase domain 15 was determined. The ETV4 protein was localised to nuclei of spermatogonia and revealed an intense staining in seminoma cells. Taken together, we characterised additional transcription factors and spermatogenesis-associated genes involved in the progression of seminoma.

The importance of protein profiling in the diagnosis and treatment of hematologic malignancies

“…The most widely used methods for this involve examination of differential gene expression in leukemic cells by assessing the mRNA levels in the given cells. Several successful studies reported the feasibility of this approach [22][23][24][25]. On the other hand, this methodology comes from a reductionist point of view, as it neglects the dynamic nature of protein translation and further modifications that take place beyond transcription.…”

The R-Ras interaction partner ORP3 regulates cell adhesion

“…Analysis of chromosomal abnormalities has revealed that the ORP3 (OSBPL3 -HGNC database) gene region in chromosome 7 is often gained and overexpressed in colon tumors and osteosarcoma (Ozaki et al, 2003;Staub et al, 2006;Tsafrir et al, 2006). Increased expression of ORP3 mRNA has frequently been reported in B-cell-associated malignancies (Ando et al, 2003;Sander et al, 2005;Chng et al, 2006;Ek et al, 2006) and testicular cancer (Sperger et al, 2003;Yamada et al, 2004;Almstrup et al, 2005;Gashaw et al, 2005;Juric et al, 2005). In a prospective study of patients with diffuse large B-cell lymphoma (DLBCL), high ORP3 expression was associated with increased mortality (Ando et al, 2003).…”

Endocrine disruptors, gene deregulation and male germ cell tumors

“…During the differentiation process, germ cells gradually lose expression of NANOG, PLAP, and POU5F1, partially of KIT and SALL4, and acquire expression of other genes including MAGE4A, and TSPY (Cao et al, 2009). Gene signature of deregulation in TGCTs respect to normal male germ cells has been reported based on array analysis in different histological entities of TGCTs (Okada et al, 2003;Gashaw et al, 2005). These studies have associated patterns of deregulation of specific genes as potential molecular markers of gene expression that define types of TGCTs and prognosis of such tumors (Gashaw et al, 2005).…”

“…Gene signature of deregulation in TGCTs respect to normal male germ cells has been reported based on array analysis in different histological entities of TGCTs (Okada et al, 2003;Gashaw et al, 2005). These studies have associated patterns of deregulation of specific genes as potential molecular markers of gene expression that define types of TGCTs and prognosis of such tumors (Gashaw et al, 2005). One feature that could define the fetal origin of TGCTs is the similarity of the patterns of gene expression between PGCs/gonocytes and neoplasic cells of testicular tumors (Almstrup et al, 2004).…”