Sipos Eva, Hegyi Kata, Treszl Andrea, Steiber Zita, Mehes Gabor, Dobos Nikoletta, Fodor Klara, Olah Gabor, Szekvolgyi Lorant, Schally Andrew V, Halmos Gabor
Department of Biopharmacy, University of Debrecen, 4032 Debrecen, Hungary.
Department of Pathology, University of Debrecen, 4032 Debrecen, Hungary.
Oncol Rep. 2017 Apr;37(4):1927-1934. doi: 10.3892/or.2017.5496. Epub 2017 Mar 8.
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.
葡萄膜黑色素瘤（UM）是最常见的原发性眼内恶性肿瘤，预后很差。UM中最常见的染色体畸变是3号染色体单体性。此前，我们证明约50%的UM表达促黄体生成素释放激素I型受体（LH-RH-R）。编码LH-RH-R的基因位于4号染色体（位置：4q21.2）；然而，UM中4号染色体数目畸变的发生情况从未被研究过。在本研究中，我们调查了3号和4号染色体的异常情况、它们之间以及与LH-RH-R表达之间的可能相关性。摘除眼球后获取了46份UM标本。通过荧光原位杂交（FISH）研究3号和4号染色体的数目畸变。仅在14份（30%）样本中检测到4号染色体正常双亲二体；然而，32例（70%）显示每个细胞核有超过2个信号。16份（35%）样本中可发现3号染色体单体性。在6份标本（13%）中发现3号染色体有超过2份拷贝，而24份（52%）样本检测到正常双亲二体。统计分析表明3号和4号染色体的拷贝数之间存在统计学显著相关性（p<0.05）。此外，不同病理特征的UM患者生存率存在中度差异。未发现染色体畸变与LH-RH-R表达之间存在相关性。我们的结果清楚地证明了人UM中3号和4号染色体的异常以及3号染色体单体性的发生率。总之，我们的结果为该肿瘤的遗传背景提供了新的见解。我们的发现有助于更精确地确定人UM的预后，并有助于开发针对这种恶性肿瘤的新治疗方法。
