Homozygous Deletions within Human Chromosome Band 9p21 in Melanoma

Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were a...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 21; pp. 10557 - 10561
Main Authors:	Fountain, Jane W., Karayiorgou, Maria, Ernstoff, Marc S., Kirkwood, John M., Vlock, Daniel R., Titus-Ernstoff, Linda, Bouchard, Bridgitte, Vijayasaradhi, Setaluri, Houghton, Alan N., Lahti, Jill, Kidd, Vincent J., Housman, David E., Dracopoli, Nicholas C.
Format:	Journal Article
Language:	English
Published:	Washington, DC National Academy of Sciences of the United States of America 01-11-1992 National Acad Sciences National Academy of Sciences
Subjects:	Alleles Base Sequence beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase - genetics Biological and medical sciences Cell Line Cell lines chromosome 9 Chromosome Banding Chromosome Deletion Chromosomes Chromosomes, Human, Pair 9 deletion Dermatology DNA, Neoplasm - genetics DNA, Neoplasm - isolation & purification Genes Genetic loci Genetic Markers Genomics Homozygote Humans Hybrid cells Interferon-alpha - genetics Interferon-beta - genetics man Medical research Medical sciences Melanoma Melanoma - genetics Melanoma - surgery Membrane Glycoproteins Molecular Sequence Data Multigene Family Oligodeoxyribonucleotides Oxidoreductases Polymerase Chain Reaction - methods Proteins - genetics Skin cancer Tumor cell line Tumors Tumors of the skin and soft tissue. Premalignant lesions Human Skin disease Genetic marker Malignant tumor Flanking sequence C9-Chromosome Gene Malignant melanoma Gene rearrangement Deletion Interferon Skin Mutation Tumor suppressor gene
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Summary:	Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the β-interferon (IFNB1) locus, the α-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4β-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumorsuppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.89.21.10557