Cytogenetics of spermatocytic tumors with a discussion of gain of chromosome 12p in anaplastic variants

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Most spermatocytic tumors (STs) have an excellent prognosis. In rare instances, metastatic disease has been documented. However, it is unclear if aggressive tumors have specific molecular alterations. Herein, we have studied primary STs with (n = 4) and without (n = 3) anaplastic features, including single-nucleotide polymorphism microarrays for 5 ST (nonanaplastic: 3; anaplastic: 2). The mean age at orchiectomy and tumor size was 49 years and 6.5 cm, respectively. Lymphovascular invasion and necrosis were identified in 3 (of 4, 75%) anaplastic STs, including one with clinically metastatic disease and one with locally aggressive disease. None of the cases in this study exhibited sarcomatoid change. The mean mitotic count was higher in anaplastic tumors (59/10 versus 10/10 high-power fields). All STs in this study were positive for SALL4 and CD117 and negative for OCT3/4 and CD30 (7/7, 100%). SSX-C positivity was identified in all but the locally aggressive anaplastic ST (5 of 6, 83%). All STs showed a consistent gain of chromosome 9 including the locus for the DMRT1 gene (5 of 5 cases, 100%), while gains of chromosome 12p were only seen in 2 (of 2) anaplastic variants. Gains of 12p in anaplastic STs may represent a biomarker of transformation into more aggressive tumors. Alternatively, STs with gain of 12p may represent an intermediate state between type II and type III germ cell tumors. Future studies are needed to validate whether gain of 12p is a consistent feature of STs with anaplastic morphology and its association with aggressive clinical behavior.

Related collections

Most cited references 15

Record: found
Abstract: found
Article: not found

Human germ cell tumours from a developmental perspective

J. Wolter Oosterhuis, Leendert H. J. Looijenga (2019)

Human germ cell tumours (GCTs) are derived from stem cells of the early embryo and the germ line. They occur in the gonads (ovaries and testes) and also in extragonadal sites, where migrating primordial germ cells are located during embryogenesis. This group of heterogeneous neoplasms is unique in that their developmental potential is in effect determined by the latent potency state of their cells of origin, which are reprogrammed to omnipotent, totipotent or pluripotent stem cells. Seven GCT types, defined according to their developmental potential, have been identified, each with distinct epidemiological and (epi)genomic features. Heritable predisposition factors affecting the cells of origin and their niches likely explain bilateral, multiple and familial occurrences of the different types of GCTs. Unlike most other tumour types, GCTs are rarely caused by somatic driver mutations, but arise through failure to control the latent developmental potential of their cells of origin, resulting in their reprogramming. Consistent with their non-mutational origin, even the malignant tumours of the group are characterized by wild-type TP53 and high sensitivity for DNA damage. However, tumour progression and the rare occurrence of treatment resistance are driven by embryonic epigenetic state, specific (sub)chromosomal imbalances and somatic mutations. Thus, recent progress in understanding GCT biology supports a comprehensive developmental pathogenetic model for the origin of all GCTs, and provides new biomarkers, as well as potential targets for treatment of resistant disease.

0 comments Cited 94 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene.

Jenny van Odijk, Renee Pera, Ellen Hansen-van der Meer … (2006)

Spermatocytic seminomas are solid tumors found solely in the testis of predominantly elderly individuals. We investigated these tumors using a genome-wide analysis for structural and numerical chromosomal changes through conventional karyotyping, spectral karyotyping, and array comparative genomic hybridization using a 32 K genomic tiling-path resolution BAC platform (confirmed by in situ hybridization). Our panel of five spermatocytic seminomas showed a specific pattern of chromosomal imbalances, mainly numerical in nature (range, 3-24 per tumor). Gain of chromosome 9 was the only consistent anomaly, which in one case also involved amplification of the 9p21.3-pter region. Parallel chromosome level expression profiling as well as microarray expression analyses (Affymetrix U133 plus 2.0) was also done. Unsupervised cluster analysis showed that a profile containing transcriptional data on 373 genes (difference of > or = 3.0-fold) is suitable for distinguishing these tumors from seminomas/dysgerminomas. The diagnostic markers SSX2-4 and POU5F1 (OCT3/OCT4), previously identified by us, were among the top discriminatory genes, thereby validating the experimental set-up. In addition, novel discriminatory markers suitable for diagnostic purposes were identified, including Deleted in Azospermia (DAZ). Although the seminomas/dysgerminomas were characterized by expression of stem cell-specific genes (e.g., POU5F1, PROM1/CD133, and ZFP42), spermatocytic seminomas expressed multiple cancer testis antigens, including TSP50 and CTCFL (BORIS), as well as genes known to be expressed specifically during prophase meiosis I (TCFL5, CLGN, and LDHc). This is consistent with different cells of origin, the primordial germ cell and primary spermatocyte, respectively. Based on the region of amplification defined on 9p and the associated expression plus confirmatory immunohistochemistry, DMRT1 (a male-specific transcriptional regulator) was identified as a likely candidate gene for involvement in the development of spermatocytic seminomas.

0 comments Cited 44 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Molecular inversion probes: a novel microarray technology and its application in cancer research.

Yuker Wang, MariEllen Cottman, Joshua Schiffman (2012)

The molecular inversion probe (MIP) assay technology was originally developed for single nucleotide polymorphism (SNP) genotyping, but has subsequently been used for identifying other types of genetic variation including focal insertions and deletions, larger copy number alterations (CNAs), loss of heterozygosity (LOH), and most recently, for somatic mutation detection. The assay requires as little as 75 ng of genomic DNA and has been shown to perform well with highly degraded DNA, such as that from formalin-fixed paraffin-embedded (FFPE)-preserved samples from 20 years ago or older. Central to the MIP assay technology are the padlock probes that hybridize to the DNA target of interest before polymerase chain reaction amplification, leading to high assay specificity. As outlined in this review, the MIP assay has enabled new discoveries and a deeper understanding of the molecular basis of cancer and its various disease subtypes. The use of novel genomic technology such as MIPs on clinically archived FFPE samples has the potential to lead to more accurate disease diagnosis, prognosis, and novel therapeutic intervention. This review describes the initial history of MIP technology, details of the MIP assay, its current analysis techniques, and recent publications related to this novel platform. Copyright © 2012 Elsevier Inc. All rights reserved.