Molecular Genetic Parameters in Pathogenesis and Prognosis of Testicular Germ Cell Tumors

Heidenreich, Axel; Srivastava, Shiv; Moul, Judd W.; Hofmann, R.

doi:10.1159/000020128

Cited by 26 publications

(12 citation statements)

References 81 publications

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“…However, most TGCTs have an increased copy number of 12p, either in the form of multiple copies of i(12p) or as tandem duplications of 12p (Dmitrovsky et al, 1990;Chaganti and Houldsworth, 2000;Heidenreich et al, 2000). Further, this chromosomal abnormality is present in the early premalignant carcinoma in situ lesions of TGCT patients (Vos et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

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Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma

et al. 2002

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Section: Discussionmentioning

confidence: 99%

“…Despite recent progress, the molecular basis for germ cell tumorigenesis is poorly understood (Heidenreich et al, 2000). Embryonal carcinoma (EC) cells are the stem cell of nonseminomatous TGCTs (Chaganti and Houldsworth, 2000).…”

Section: Introductionmentioning

confidence: 99%

Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma

et al. 2002

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“…In addition to the characteristic cytogenetic aberration isochromosome 12p, a number of recurrent DNA sequence changes and chromosome aberrations have been found in TGCT (Atkin and Baker, 1982;Castedo et al, 1989a,b;Heidenreich et al, 2000;Lothe et al, 1993;Murty and Chaganti, 1998;Skotheim et al, 2001a). Nevertheless only few genes contributing to the development of this disease have been identified (Looijenga et al, 1999;Kraggerud et al, 2002;Skotheim et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Frequent promoter hypermethylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene in testicular cancer

Smith‐Sørensen

Skotheim

et al. 2002

Oncogene

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Testicular germ cell tumours are classified into two major histological subgroups, seminomas and nonseminomas. All tumours display several recurrent chromosomal aberrations, but few target genes have been identified. Previous studies have shown that genome-wide hypermethylation of CpG islands is significantly more prevalent in nonseminomas than in seminomas. We have studied two potential target genes in testicular cancer. A series of 70 tumours were analysed for methylation of CpG sites in the O 6 -methylguanine-DNA methyltransferase (MGMT) gene promoter, and in exon 1a of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A). In addition, eight microsatellite markers within and flanking these genes at chromosome arms 10q and 9p, respectively, were analysed for allelic imbalances. Allele alterations were frequently seen at 9p loci (47 out of 70, 67%), but none of the tumours (none out of 55) showed methylation of CDKN2A. On the other hand, a high frequency of MGMT promoter methylation (32 out of 69, 46%) was found, as well as allelic imbalances at 10q markers (50 out of 70, 71%). A significantly higher methylation frequency was found in nonseminomas (24 out of 35, 69%) compared to seminomas (eight out of 33, 24%) (P=0.0003, Fisher's exact test). Immunohistochemical analysis of the MGMT protein in a subgroup (n=20) of the testicular tumours supported the hypothesis of gene silencing being the functional consequence of the promoter methylation. In summary, our data suggest that inactivation of MGMT contributes to development of nonseminomatous testicular cancer.

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“…TGCTs are the most common carcinomas of men between the ages of 15 and 35 (11). Despite recent progress, the molecular basis for germ cell tumorigenesis is poorly understood (12). In our studies the human TGCT-derived EC cell line NT2/D1 is used.…”

Section: Human Embryonal Carcinomamentioning

confidence: 99%

Retinoid Target Gene Activation during Induced Tumor Cell Differentiation: Human Embryonal Carcinoma as a Model

Spinella

Kerley

White

et al. 2003

The Journal of Nutrition

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Many agents that exhibit chemopreventive activity are able to mediate a differentiation response in premalignant and malignant tissues. One of the most widely studied classes of tumor differentiation agents is the retinoids. There is rapidly evolving evidence for beneficial retinoid actions in the prevention or treatment of clinical tumors. However, the use of retinoids in the clinic is limited by acquired resistance and toxicity, especially when administered chronically in preventive strategies. Although retinoids are known to regulate gene transcription by activating retinoid receptors, the identity of the target genes that mediate the beneficial effects of retinoids are largely unknown. Here we review a useful model of retinoid-induced tumor cell differentiation: human embryonal carcinoma. The pluripotent nature and ease of use make human embryonal carcinoma cells a valuable and practical complement to human embryonic stem cells as an in vitro model of early human development. In addition, retinoid treatment of human embryonal carcinoma is an important model of induced tumor cell differentiation because retinoids cause the reversal of the malignant phenotype coincident with terminal neuronal differentiation. We have used both de novo and candidate approaches with this system in an effort to uncover critical downstream targets of retinoid receptors during differentiation induction. J. Nutr. 133: 273S-276S, 2003.

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Molecular Genetic Parameters in Pathogenesis and Prognosis of Testicular Germ Cell Tumors

Cited by 26 publications

References 81 publications

Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma

Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma

Frequent promoter hypermethylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene in testicular cancer

Retinoid Target Gene Activation during Induced Tumor Cell Differentiation: Human Embryonal Carcinoma as a Model

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