Atypically low spontaneous sister chromatid exchange formation in uveal melanoma.
Uveal melanoma (UM) is the most common primary intraocular cancer of adults and is characterized by several well-established chromosomal changes. More recently, a specific mutation of guanine nucleotide binding protein Gq alpha subunit (GNAQ) has also been identified in a proportion of UM. Although some of these alterations have been suggested to be early changes, the genetic alterations responsible for the development of UM have yet to be clearly determined. Cancers are characterized by increased genetic instability, and analysis of established cancer cell lines and blood from cancer patients has universally been associated with an increased level of sister chromatid exchange (SCE). We have observed that the spontaneous frequency of SCE in primary cultures of UM and UM-derived cell lines is decreased below normal baseline levels, a phenomenon unique to UM when compared with multiple other cancers. This finding was specific to the tumor and not found in lymphocytes from the patients. Although we cannot exclude the possibility that low SCE (LSCE) is peculiar to the uveal melanocytes lineage, as it was consistently observed in all UM studied, regardless of other genetic defects, we propose that this phenomenon contributes to the molecular pathogenesis of UM.
Academic Unit of Ophthalmology and Orthoptics, University of Sheffield, Sheffield S10 2RX, UK.
Leslie
L
Hoh
Polly
P
Gravells
David
D
Canovas
Aliya
A
Ul-Hassan
Ian G
IG
Rennie
Helen
H
Bryant
Karen
K
Sisley
D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D006657:Histones / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D016685:Mitomycin / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics / Q000473:pathology; D000098943:Uveal Melanoma
C468783:H2AX protein, human; D006657:Histones; D016685:Mitomycin