Genome-wide methylation analysis in patients with proximal hypospadias - a pilot study and review of the literature.

In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age.

Mediastinal germ cell tumors: many questions and perhaps an answer.

Some germ cell tumors (GCTs) in men develop into hematologic malignancies; however, the clonal origins of such malignancies remain unknown. In this issue of the JCI, Taylor, Donoghue, et al. unravel the clonal relationship between primary mediastinal nonseminomas (PMNs) and hematologic somatic-type malignancies (HSTMs).

Malignant recurrence after mature Sacrococcygeal teratoma: A meta-analysis and review of the literature.

Background And Aims: Sacrococcygeal teratoma (SCT) is a rare extragonadal germ cell tumour mostly diagnosed during infancy and early childhood. Neonatal SCTs are mostly mature, but can also contain immature and/or malignant components. Recurrence of an SCT alters prognosis, especially when it is malignant, of which its mechanism is not yet fully understood.

Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors.

Novel treatment options are needed for testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing cisplatin resistance, the major cause of cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved HDAC inhibitors (HDACis), belinostat and panobinostat, in (T)GCT cell lines including those resistant to cisplatin.

Differential expression of DNA methyltransferases and demethylases among the various testicular germ cell tumor subtypes.

Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs). analysis of TCGA database, assessment of transcript levels of most relevant enzymes in four TGCT cell lines and validation in patient cohort (real-time quantitative polymerase chain reaction; immunohistochemistry). , and were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs).

Effect of neoadjuvant chemoradiotherapy on p53 and SOX2 protein expression in esophageal adenocarcinoma.

To determine if neoadjuvant chemoradiotherapy (nCRT) affects p53 and SOX2 expression in esophageal adenocarcinoma (EAC). Comparison of p53 and SOX2 expression in 100 paired pre- and post-nCRT EAC samples. Aberrant p53 was largely concordant (75/83, 90%), while 13/18 (72%) pre-nCRT samples with wild-type (WT) p53 staining, showed aberrant staining in paired post-nCRT samples.

Do pathologists agree with each other on the histological assessment of pT1b oesophageal adenocarcinoma?

Background: In early (T1) oesophageal adenocarcinoma (OAC), the histological profile of an endoscopic resection specimen plays a pivotal role in the prediction of lymph node metastasis and the potential need for oesophagectomy with lymphadenectomy.

Objective: To evaluate the inter-observer agreement of the histological assessment of submucosal (pT1b) OAC.

Methods: Surgical and endoscopic resection specimens with pT1b OAC were independently reviewed by three gastrointestinal pathologists.

Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis.

Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20-40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in situ(CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment.

Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential.

Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)).

SRY mutation analysis by next generation (deep) sequencing in a cohort of chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype.

Background: The presence of the Y-chromosome or Y chromosome-derived material is seen in 4-60% of Turner syndrome patients (Chromosomal Disorders of Sex Development (DSD)). DSD patients with specific Y-chromosomal material in their karyotype, the GonadoBlastoma on the Y-chromosome (GBY) region, have an increased risk of developing type II germ cell tumors/cancer (GCC), most likely related to TSPY. The Sex determining Region on the Y gene (SRY) is located on the short arm of the Y-chromosome and is the crucial switch that initiates testis determination and subsequent male development.

Tumor risk and clinical follow-up in patients with disorders of sex development.

A subset of patients with disorders of sex development (DSD) is at risk for malignant germ cell tumors (GCTs). The degree of gonadal differentiation (or "testicularization" in the presence of a specific part of the Y chromosome), in combination with expression of embryonic germ cell markers, and (a) Y specific gene(s) related to cell-cycle control and proliferation, determines this risk. Incompletely matured Sertoli/granulosa cells are insufficiently capable of directing the normal mitotic block/meiotic induction germ cell program, and as a result, embryonic germ cells are delayed or blocked in their normal maturation process.

Spermatocytic seminoma: toward further understanding of pathogenesis.

Human germ cell tumours comprise a heterogeneous group of neoplasms which, based on pathobiological, genetic and clinical characteristics, can be subdivided into different entities. One of these subgroups relates to the so-called spermatocytic seminomas, benign tumours only found in the testis, preferentially in elderly men. Various developmental models for this type of germ cell tumour have been proposed and it is clear that spermatocytic seminoma has a pathogenesis independent from that of seminoma.