Abstract:
PURPOSE:Recently, a segregation study in families with uveal and cutaneous melanoma identified 9q21 as a potential locus harboring a tumor-suppressor gene (TSG). One of the genes in this area, RASEF, was then analyzed as a candidate TSG, but lack of point mutations and copy number changes could not confirm this. In this study, the RASEF gene was investigated for potential mutations and gene silencing by promoter methylation in uveal melanoma. METHODS:Eleven uveal melanoma cell lines and 35 primary uveal melanoma samples were screened for mutations in the RASEF gene by high-resolution melting-curve and digestion analysis. Expression of RASEF was determined by real-time RT-PCR in all cell lines and 16 primary uveal melanoma samples, and the methylation status of the promoter of the RASEF gene was analyzed and confirmed by direct sequencing. RESULTS:Mutation screening revealed a known polymorphism (R262C; C-->T) in exon 5 of the RASEF gene that displayed a normal frequency (54%). Of the primary uveal melanomas, 46% presented a heterozygous genotype, and 10 (91%) of 11 cell lines showed a homozygous genotype. Melting-curve analysis indicated loss of heterozygosity in at least two primary tumors. Low RASEF expression in the cell lines and primary tumors correlated with methylation of the RASEF promoter region. Homozygosity and methylation of the RASEF gene in primary tumors were associated with decreased survival (P = 0.019). CONCLUSIONS:Homozygosity, in combination with methylation, appears to be the mechanism targeting RASEF in uveal melanoma, and allelic imbalance at this locus supports a TSG role for RASEF.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Maat W,Beiboer SH,Jager MJ,Luyten GP,Gruis NA,van der Velden PAdoi
10.1167/iovs.07-1135subject
Has Abstractpub_date
2008-04-01 00:00:00pages
1291-8issue
4eissn
0146-0404issn
1552-5783pii
49/4/1291journal_volume
49pub_type
杂志文章abstract:PURPOSE:We evaluated whether UVA-riboflavin collagen cross-linking (CXL) increases transverse stromal shear moduli ex vivo, whether the shear moduli are greater in the anterior compared to the posterior stroma, and whether the shear moduli are affected by CXL. METHODS:The resistance to unidirectional transverse shear ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2015-06-01 00:00:00
abstract::In the retina from an eye enucleated for choroidal melanoma apposed rod outer segments were seen by transmission electron microscopy to be fusing together in groups by the confluence of their plasma membranes and the formation of cytoplasmic bridges between adjacent outer segments. These fusions were seen in areas dis...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2002-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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journal_title:Investigative ophthalmology & visual science
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更新日期:2015-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2003-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:1995-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2011-05-06 00:00:00
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