VASA Is a Specific Marker for Both Normal and Malignant Human Germ Cells

Zeeman, Anne‐Marie; Stoop, Hans; Boter, Marjan; Gillis, Ad J. M.; Castrillón, Diego H.; Oosterhuis, J. Wolter; Looijenga, Leendert

doi:10.1038/labinvest.3780408

Cited by 67 publications

(32 citation statements)

References 44 publications

(46 reference statements)

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“…Therefore, VASA is currently the first definitive genetic marker for distinguishing fetal germ cells from hESCs [57]. As a result, identification of robust levels of VASA protein expression in CIS lends support to the hypothesis that CIS is derived from fetal germ cells that retain high levels of pluripotent stem cell gene expression as well as germ cell-identity markers including VASA [61].…”

Section: Turning Germ Cells Into Germ Cell Tumors: Elevated Expressiomentioning

confidence: 79%

The Stem Cell Identity of Testicular Cancer

Clark

2007

Stem Cell Rev

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Testicular germ cell tumors account for 1% of all cancers, and are the most common malignancies to affect males between the ages of 15 and 34. Understanding the pathogenesis of testis cancer has been challenging because the molecular and cellular events that result in the formation of germ cell tumors are hypothesized to occur during human fetal development. In this review, the molecular pathways involved in human testis cancer will be presented based on our research in human embryonic stem cells (hESCs), and also research using animal models. Testis germ cell tumors are unique in that the normal germ cell from which the tumor is derived has distinct stem cell characteristics that are shared with pluripotent hESCs. In particular, normal fetal germ cells express the core pluripotent transcription factors NANOG, SOX2 and OCT4. In contrast to hESCs, the germ line is not pluripotent. As a result, germ cell tumorigenesis may arise from loss of germ line-specific inhibitors which in normal germ cells prevent overt pluripotency and self-renewal and when absent in abnormal germ cells, result in the conversion to germ line cancer stem cells. At the conclusion of this review, a model for the molecular events involved in germ cell tumor formation and the relationship between germ cell tumorigenesis and stem cell biology will be presented.

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Section: Turning Germ Cells Into Germ Cell Tumors: Elevated Expressiomentioning

confidence: 79%

The Stem Cell Identity of Testicular Cancer

Clark

2007

Stem Cell Rev

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“…Spermatocytic seminoma may be confused with classical seminoma; the distinction is important from the clinical standpoint because spermatocytic seminoma virtually never metastasises [20,29,56] and requires no treatment besides orchiectomy [7,14,33,45,47,53,57]. Recent immunohistochemical and molecular studies [42,51,59] have demonstrated a different origin for seminoma/ dysgerminoma and spermatocytic seminoma. Seminoma/ dysgerminoma originates from an embryonic germ cell, whilst the cell of origin of spermatocytic seminoma is at least capable of maturing to the stage of spermatogoniapachytene spermatocyte.…”

Section: Discussionmentioning

confidence: 98%

Intermitochondrial cement (nuage) in a spermatocytic seminoma: comparison with classical seminoma and normal testis

et al. 2008

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The nuage, an ultrastructural marker of normal human germ cells (spermatogonia type A and primary spermatocytes), may be found associated with mitochondria (intermitochondrial cement) and/or free in the cytoplasm. Eight specimens from germ cell-related tumours were reviewed to assess whether the nuage could have diagnostic significance in testicular neoplasms. The nuage of neoplastic cells from seven classical seminomas and one spermatocytic seminoma was compared with that from two normal testes. The ultrastructural study demonstrated that only spermatocytic seminoma cells contained both types of nuage and that significantly fewer spermatocytic seminoma cells (28%) contained intermitochondrial cement compared with control spermatogonia type A (81.1%) and primary spermatocytes (47.6%). The data indicate that (1) the detection of the nuage confirms that the phenotype of spermatocytic seminoma is more differentiated than that of classical seminoma; (2) the intermitochondrial cement is an additional example of how a distinctive organelle of a normal cell is preserved in its neoplastic counterpart and (3) if the intermitochondrial cement were found in other cases of spermatocytic seminoma, this organelle of the normal germ cell lineage could be considered as a new ultrastructural marker of the neoplasm.

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“…Third, they may differentiate into Oct4 and MVH-negative tissues. In nonseminomatous GCTs including teratomas, germ cells have variable or no expression of Oct4 or Vasa (Honecker et al, 2006, Zeeman et al, 2002. Lastly, they could differentiate into somatic lineages.…”

Section: Discussionmentioning

confidence: 99%

The distribution and behavior of extragonadal primordial germ cells in Bax mutant mice suggest a novel origin for sacrococcygeal germ cell tumors

Runyan

Gu²,

Shoemaker³

et al. 2008

Int. J. Dev. Biol.

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In the mouse, germ cells that do not reach the genital ridges rapidly die by a wave of apoptosis that requires the pro-apoptotic protein Bax. In Bax-null embryos, large numbers of ectopic (extragonadal) germ cells fail to die. We have studied the fates of these, in an effort to understand the etiology of human extragonadal germ cell tumors, which are thought to arise from ectopic germ cells. We find that ectopic germ cells in which apoptosis is blocked form a heterogeneous population, which partially differentiates along the gonocyte pathway to different extents in different regions of the embryo, and in the two genders. In particular, a previously undescribed population of ectopic germ cells was identified in the tail. These germ cells retained primitive markers for longer than ectopic germ cells in other regions, and represent a possible origin for sacrococcygeal type I extragonadal germ cell tumors found in neonates and infants. This hypothesis is supported, but not proved, by the finding of cells expressing the germ cell marker Oct4 associated with a coccygeal germ cell tumor in a human infant.

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VASA Is a Specific Marker for Both Normal and Malignant Human Germ Cells

Cited by 67 publications

References 44 publications

The Stem Cell Identity of Testicular Cancer

The Stem Cell Identity of Testicular Cancer

Intermitochondrial cement (nuage) in a spermatocytic seminoma: comparison with classical seminoma and normal testis

The distribution and behavior of extragonadal primordial germ cells in Bax mutant mice suggest a novel origin for sacrococcygeal germ cell tumors

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