Allelic deletions in the long arm of chromosome 12 identify sites of candidate tumor suppressor genes in male germ cell tumors Journal Article

   

Authors:	Murty, V. V. V. S.; Houldsworth, J.; Baldwin, S.; Reuter, V.; Hunziker, W.; Besmer, P.; Bosl, G.; Chaganti, R. S. K.
Article Title:	Allelic deletions in the long arm of chromosome 12 identify sites of candidate tumor suppressor genes in male germ cell tumors
Abstract:	Human male germ cell tumors (GCTs) result from malignant transformation of premeiotic or early meiotic germ cells and exhibit embryonal-like differentiation of the three germinal layers. The genetic basis of origin and expression of differentiated phenotypes by GCTs are poorly understood. Our recent cytogenetic analysis of a large series of GCTs has shown that two chromosome 12 abnormalities, an isochromosome for the short arm [i(12p)] and deletions in the long arm [del(12q)], characterize these tumors, which led us to suggest that the deletions represent loss of one or more candidate tumor suppressor genes whose products regulate the normal proliferation of the spermatogonial stem cells. We undertook a molecular mapping of the deletions by comparing germ-line and tumor genotypes of eight polymorphic loci in paired normal/tumor DNA samples from 45 GCT patients. Analysis of loss of constitutional heterozygosity at these loci revealed two regions of frequent loss (>40%), one at 12q13 and the other at 12q22, identifying the sites of the postulated tumor suppressor genes. One tumor (no. 143A) exhibited a homozygous deletion of a region of 12q22, which included the MGF gene. The KIT and MGF genes have been shown to play key roles in embryonal and postnatal development of germ cells; therefore, we evaluated their expression by Northern blot analysis in a panel of three GCT cell lines and 24 fresh GCT biopsies. Deregulated expression of MGF and KIT, which was discordant between seminomatous and nonseminomatous lesions, was observed.
Keywords:	clinical article; human tissue; human cell; gene deletion; allele; gene expression; cell growth; cell line; genotype; alleles; cell transformation, neoplastic; tumor suppressor gene; dna; dna, neoplasm; testicular neoplasms; teratoma; neoplasms, germ cell and embryonal; chromosome deletion; germ cell tumor; blotting, northern; chromosome 12q; genes, tumor suppressor; northern blotting; southern blotting; restriction mapping; chromosome banding; chromosomes, human, pair 12; dna probes; blotting, southern; human; male; priority journal; article; polymorphism (genetics); support, u.s. gov't, p.h.s.
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	89
Issue:	22
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	1992-11-15
Start Page:	11006
End Page:	11010
Language:	English
DOI:	10.1073/pnas.89.22.11006
PUBMED:	1332066
PROVIDER:	scopus
PMCID:	PMC50472
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026454815&doi=10.1073%2fpnas.89.22.11006&partnerID=40&md5=c90623632407af6dc54dc500e7d0f7c5
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/150014