Koroknai Viktória, Ecsedi Szilvia, Vízkeleti Laura, Kiss Tímea, Szász István, Lukács Andrea, Papp Orsolya, Ádány Róza, Balázs Margit
aDepartment of Preventive Medicine, Faculty of Public Health bMTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary.
Melanoma Res. 2016 Apr;26(2):100-7. doi: 10.1097/CMR.0000000000000227.
Malignant melanoma is one of the most aggressive human cancers. Invasion of cells is the first step in metastasis, resulting in cell migration through tissue compartments. We aimed to evaluate genomic alterations specifically associated with the invasive characteristics of melanoma cells. Matrigel invasion assays were used to determine the invasive properties of cell lines that originated from primary melanomas. Array comparative genomic hybridization analyses were carried out to define the chromosome copy number alterations (CNAs). Several recurrent CNAs were identified by array comparative genomic hybridization that affected melanoma-related genes. Invasive primary cell lines showed high frequencies of CNAs, including the loss of 7q and gain of 12q chromosomal regions targeting PTPN12, ADAM22, FZD1, TFPI2, GNG11, COL1A2, SMURF1, VGF, RELN and GLIPR1 genes. Gain of the GDNF (5p13.1), GPAA1, PLEC and SHARPIN (8q24.3) genes was significantly more frequent in invasive cell lines compared with the noninvasive ones. Importantly, copy number gains of these genes were also found in cell lines that originated from metastases, suggesting their role in melanoma metastasis formation. The present study describes genomic differences between invasive and noninvasive melanoma cell lines that may contribute toward the aggressive phenotype of human melanoma cells.
恶性黑色素瘤是最具侵袭性的人类癌症之一。细胞侵袭是转移的第一步，导致细胞通过组织间隙迁移。我们旨在评估与黑色素瘤细胞侵袭特性特异性相关的基因组改变。使用基质胶侵袭试验来确定源自原发性黑色素瘤的细胞系的侵袭特性。进行了阵列比较基因组杂交分析以确定染色体拷贝数改变（CNA）。通过阵列比较基因组杂交鉴定了几种影响黑色素瘤相关基因的复发性CNA。侵袭性原代细胞系显示出高频率的CNA，包括7号染色体长臂缺失和12号染色体长臂增加，靶向PTPN12、ADAM22、FZD1、TFPI2、GNG11、COL1A2、SMURF1、VGF、RELN和GLIPR1基因。与非侵袭性细胞系相比，侵袭性细胞系中GDNF（5p13.1）、GPAA1、PLEC和SHARPIN（8q24.3）基因的增加明显更频繁。重要的是，在源自转移灶的细胞系中也发现了这些基因的拷贝数增加，表明它们在黑色素瘤转移形成中的作用。本研究描述了侵袭性和非侵袭性黑色素瘤细胞系之间的基因组差异，这些差异可能导致人类黑色素瘤细胞的侵袭性表型。
