Allelic loss and somatic differentiation in human male germ cell tumors Journal Article


Authors: Murty, V. V. V. S.; Bosl, G. J.; Houldsworth, J.; Meyers, M.; Mukherjee, A. B.; Reuter, V.; Chaganti, R. S. K.
Article Title: Allelic loss and somatic differentiation in human male germ cell tumors
Abstract: The complex but poorly Understood human male germ cell tumors offer unusual opportunities for the genetic analysis of malignant transformation and embryonal differentiation in a pluripotential stem cell lineage. Histologically, these tumors are divided into two major subgroups, seminomas which are characterized by inability to express embryonal differentiation, and non-seminomas which are characterized by ability to express embryonal as well as extraembryonal patterns of differentiation. To understand the role of genetic factors in the development of these tumors and the regulation of differentiation expressed by them, we carried out a detailed allelotype analysis by the loss of heterozygosity assay. This analysis revealed frequent deletions in known tumor suppressor genes (RB1, DCC, NME), a number of previously described sites of candidate tumor suppressor genes (3p, 9p, 9q, 10q, 11p, 11q and 17p), as well as several novel sites (2p, 3q, 5p, 12q, 18p and 20p). Our results also showed that well differentiated teratomas exhibit a significantly higher level of allelic loss compared to the less differentiated embryonal carcinomas. In addition, certain loci and genes exhibited frequent non-random deletion in teratomas (D3S32, D3S42, D5S12, D10S25, D11S12, RB1, TP53, NME1, NME2, D17S4, D18S6 and D20S6) and embryonal carcinomas (1FNB, D9S27). Among these loci, the NME genes were notable for a high degree of genetic loss (> 70%) in teratomas. These results suggested that nonrandom loss or inactivation of certain genes may be associated with tumor development and loss or inactivation of other genes may be associated with somatic differentiation.
Keywords: human tissue; human cell; major clinical study; proto-oncogene proteins; allele; proto-oncogene proteins c-kit; alleles; cell differentiation; tumor suppressor gene; heterozygosity; gene loss; teratoma; receptor protein-tyrosine kinases; chromosome deletion; malignant transformation; germ cell tumor; embryonal carcinoma; genes, tumor suppressor; deletion mutant; proto-oncogenes; germinoma; humans; human; male; priority journal; article; receptors, colony-stimulating factor
Journal Title: Oncogene
Volume: 9
Issue: 8
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 1994-08-01
Start Page: 2245
End Page: 2251
Language: English
PROVIDER: scopus
PUBMED: 7518576
DOI/URL:
Notes: Export Date: 14 January 2019 -- Article -- CODEN: ONCNE C2 -- Source: Scopus
Citation Impact
MSK Authors
  1. Victor Reuter
    1228 Reuter
  2. Raju S K Chaganti
    391 Chaganti
  3. George Bosl
    430 Bosl
  4. Michael L Meyers
    16 Meyers
  5. Vundavalli V. V. S. Murty
    53 Murty