Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

Sipos,Eva; Hegyi,Kata; Treszl,Andrea; Steiber,Zita; Mehes,Gabor; Dobos,Nikoletta; Fodor,Klara; Olah,Gabor; Szekvolgyi,Lorant; Schally,Andrew  V.; Halmos,Gabor

doi:10.3892/or.2017.5496

Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

Authors:
- Eva Sipos
- Kata Hegyi
- Andrea Treszl
- Zita Steiber
- Gabor Mehes
- Nikoletta Dobos
- Klara Fodor
- Gabor Olah
- Lorant Szekvolgyi
- Andrew V. Schally
- Gabor Halmos
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Affiliations: Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary, Department of Pathology, University of Debrecen, 4032 Debrecen, Hungary, Department of Ophthalmology, University of Debrecen, 4032 Debrecen, Hungary, 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, Endocrine, Polypeptide and Cancer Institute and South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center, Miami, FL 33125, USA
Published online on: March 8, 2017 https://doi.org/10.3892/or.2017.5496
Pages: 1927-1934
Copyright: © Sipos et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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