| Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. | |
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MedLine Citation:
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PMID: 16540528 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Carcinoma in situ testis (CIS), also known as intratubular germ cell neoplasia (ITGCN), is a pre-invasive precursor of testicular germ cell tumours, the commonest cancer type of male adolescents and young adults. In this review, evidence supporting the hypothesis of developmental origin of testicular germ cell cancer is summarized, and the current concepts regarding aetiology and pathogenesis of this disease are critically discussed. Comparative studies of cell surface proteins (e.g. PLAP and KIT), some of the germ cell-specific markers (e.g. MAGEA4, VASA, TSPY and NY-ESO-1), supported by studies of regulatory elements of the cell cycle (e.g. p53, CHK2 and p19-INK4d) demonstrated a close similarity of CIS to primordial germ cells and gonocytes, consistent with the pre-meiotic origin of CIS. Recent gene expression profiling studies showed that CIS cells closely resemble embryonic stem cells (ESCs). The abundance of factors associated with pluripotency (NANOG and OCT-3/4) and undifferentiated state (AP-2gamma) may explain the remarkable pluripotency of germ cell neoplasms, which are capable of differentiating to various somatic tissue components of teratomas. Impaired gonadal development resulting in the arrest of gonocyte differentiation and retention of its embryonic features, associated with an increasing genomic instability, is the most probable model for the pathogenesis of CIS. Genomic amplification of certain chromosomal regions, e.g. 12p, may facilitate survival of CIS and further invasive progression. Genetic studies, have so far not identified gene polymorphisms predisposing to the most common non-familial testicular cancer, but this research has only recently begun. Association of CIS with other disorders, such as congenital genital malformations and some forms of impaired spermatogenesis, all rising in incidence in a synchronous manner, led to the hypothesis that CIS might be a manifestation of testicular dysgenesis syndrome (TDS). The aetiology of TDS including testicular cancer remains to be elucidated, but epidemiological trends suggest a primary role for environmental factors, probably combined with genetic susceptibility. |
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Authors:
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Ewa Rajpert-De Meyts |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2006-03-15 |
Journal Detail:
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Title: Human reproduction update Volume: 12 ISSN: 1355-4786 ISO Abbreviation: Hum. Reprod. Update Publication Date: 2006 May-Jun |
Date Detail:
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Created Date: 2006-04-07 Completed Date: 2006-06-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9507614 Medline TA: Hum Reprod Update Country: England |
Other Details:
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Languages: eng Pagination: 303-23 Citation Subset: IM |
Affiliation:
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University Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark. erm@rh.hosp.dk |
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| MeSH Terms | |
Descriptor/Qualifier:
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Carcinoma in Situ
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genetics,
pathology* Cell Transformation, Neoplastic / genetics* Environment Gonadal Dysgenesis / genetics Humans Male Models, Biological* Neoplasms, Germ Cell and Embryonal / etiology*, genetics, pathology Polymorphism, Genetic Testicular Neoplasms / etiology*, genetics, pathology |
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