In situ hybridization localizes the human putative oncogene GLI to chromosome subbands 12q13.3?14.1

Arheden, Kristina; Rønne, Mogens; Mandahl, Nils; Heim, Sverre; Kinzler, Kenneth W.; Vogelstein, Bert; Mitelman, Felix

doi:10.1007/bf00288260

Cited by 39 publications

(14 citation statements)

References 19 publications

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“…In humans, PAH maps to 12q22-q24, IGFI maps to 12q22-q24. 1, IFG maps to 12q24, and GLI maps to 12q13-q14 (30,(36)(37)(38). The assignment ofD12S53Eh distal to these markers extends this region of known homology on mouse chromosome 10.…”

Section: Discussionmentioning

confidence: 66%

A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12.

Kwon

Chintamaneni

Kozak

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

148

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A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12 ( ABSTRACTMelanocytes preferentially express an mRNA species, Pmel 17, whose protein product cross-reacts with anti-tyrosinase antibodies and whose expression correlates with the melanin content. We have now analyzed the deduced protein structure and mapped its chromosomal location in mouse and human. The amino acid sequence deduced from the nucleotide sequence of the Pmel 17 cDNA showed that the protein is composed of 645 amino acids with a molecular weight of 68,600. The Pmel 17 protein contains a putative leader sequence and a potential membrane anchor segment, which indicates that this may be a membrane-associated protein in melanocytes. The deduced protein contains five potential N-glycosylation sites and relatively high levels of serine and threonine. Three repeats of a 26-amino acid motif appear in the middle of the molecule. The human Pmel 17 gene, designated D12S53E, maps to chromosome 12, region 12pter-q21; and the mouse homologue, designated D12S53Eh, maps to the distal region of mouse chromosome 10, a region also known to carry the coat color locus si (silver).

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Section: Discussionmentioning

confidence: 66%

A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12.

Kwon

Chintamaneni

Kozak

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

148

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“…The INT] (WNTJ), GLI, and MDM2 genes have been mapped to the 12ql3-ql4 region (31)(32)(33). While neither INTl nor GLI were seen to be rearranged in myxoid liposarcomas by Southern blot analysis (34), pulsed field mapping of 600 kilobases of DNA surrounding the GLI locus showed a specific alteration in the restriction pattern due to methylation differences unique to myxoid liposarcomas (35).…”

Section: Discussionmentioning

confidence: 99%

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

Murty

Houldsworth

Baldwin

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

108

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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 orign 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)J 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 offrequent 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.

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“…Subsequently, the GLI gene has been found to be amplified in other human glioblastomas and in some liposarcomas, osteosarcomas, and teratocarcinomas (20,30; unpublished observations). The GLI gene locus has been localized to 12q13.3 to 14.1, a region frequently translocated in human lipomas, myxoid liposarcomas, uterine leiomyomas, and pleomorphic adenomas of the salivary gland (1,8).…”

mentioning

confidence: 99%

The GLI gene encodes a nuclear protein which binds specific sequences in the human genome.

Kinzler¹,

Vogelstein²

1990

Mol. Cell. Biol.

450

331

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The GLI gene is amplified in a subset of human tumors and encodes a protein product with five zinc finger DNA-binding motifs. In this study, we show that the GLI gene product has a predominantly nuclear localization and binds DNA in a sequence-specific fashion. Three GLI binding sites were identified by using a novel procedure in which total human DNA was bound to a GLI recombinant fusion protein, and the polymerase chain reaction was used to amplify and recover the bound sequences. The GLI protein protected a 23-to 24-base region within all three binding sites, and the protected region in each case included the 9-base-pair sequence 5'-GACCACCCA-3'. One of the binding sites was contained within a 63-base-pair repeat of the variable number of tandem repeat type, whereas the other two sites were represented once in the genome. The approach used here to identify GLI binding sites should be applicable to the characterization of other zinc finger proteins.

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In situ hybridization localizes the human putative oncogene GLI to chromosome subbands 12q13.3?14.1

Cited by 39 publications

References 19 publications

A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12.

A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12.

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

The GLI gene encodes a nuclear protein which binds specific sequences in the human genome.

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