title: Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma.
abstract: Uveal melanoma (UM) is the most common primary intraocular malignancy with a very poor prognosis. The most frequent chromosome aberration in UM is the monosomy of chromosome 3. Previously, we demonstrated that ~50% of UMs express type-I receptor for luteinizing hormone‑releasing hormone (LH-RH-R). The gene encoding LH-RH-R is located in chromosome 4 (location: 4q21.2); however, the occurrence of numerical aberrations of chromosome 4 have never been studied in UM. In the present study, we investigated the abnormalities of chromosome 3 and 4, and the possible correlation between them, as well as with LH-RH-R expression. Forty-six specimens of UM were obtained after enucleation. Numerical aberrations of chromosome 3 and 4 were studied by fluorescence in situ hybridization (FISH). Chromosome 4 was detected in normal biparental disomy only in 14 (30%) samples; however, 32 cases (70%) showed more than 2 signals/nucleus. Monosomy of chromosome 3 could be found in 16 (35%) samples. In 6 specimens (13%), more than 2 copies of chromosome 3 were found, while normal biparental disomy was detected in 24 (52%) samples. Statistical analysis indicated a statistically significant (p<0.05) correlation between the copy number of chromosome 3 and 4. Moreover, moderate difference was revealed in the survival rate of the UM patients with various pathological profiles. No correlation was found between chromosome aberrations and LH-RH-R expression. Our results clearly demonstrate abnormalities in chromosome 3 and 4 and the incidence of the monosomy of chromosome 3 in human UM. In summary, our results provide new incite concerning the genetic background of this tumor. Our findings could contribute to a more precise determination of the prognosis of human UM and to the development of new therapeutic approaches to this malignancy.
authors.affiliation: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Sipos
authors.affiliation: Department of Pathology, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Hegyi
authors.affiliation: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Treszl
authors.affiliation: Department of Ophthalmology, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Steiber
authors.affiliation: Department of Pathology, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Mehes
authors.affiliation: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Dobos
authors.affiliation: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Klara
authors.initials: K
authors.lastname: Fodor
authors.affiliation: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Olah
authors.affiliation: MTA-DE Momentum, Genome Architecture and Recombination Research Group, Research Centre for Molecular Medicine; Department of Biochemistry and Molecular Biology, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Lorant
authors.initials: L
authors.lastname: Szekvolgyi
authors.affiliation: Endocrine, Polypeptide and Cancer Institute and South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center, Miami, FL 33125, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.affiliation: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Halmos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D011966:Receptors, LHRH; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: D011966:Receptors, LHRH