Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization
Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization
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DOI：
10.1002/cyto.1131
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发表时间：
2001-08-15
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影响因子：
--
通讯作者：
Adány, R
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文献类型：
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作者：
Balázs, M;Adám, Z;Adány, R
恶性黑色素瘤转移进展的特征性遗传变化尚不完全清楚。本研究的目的是探讨与这种肿瘤的侵袭行为相关的特定染色体改变。进行比较基因组杂交以筛选和比较原发性和转移性黑色素瘤中存在的基因组不平衡。分析了16份原发性和12份转移性标本。我们发现两个亚组的染色体畸变模式相似;然而，也发现了仅存在于原发性和/或转移性肿瘤中的改变。原发性和转移性病变的平均遗传变化数分别为6.3（范围1-14）和7.8（范围1-16）。9 p和10 q的丢失频率最高，而1 q、6 p、7 q和8 q的丢失频率最高。在两种肿瘤类型中，不同的高水平扩增定位于1 p12-p21和1 p22-p31。4 q12-q13.1、7q21.3-qter和8 q23-qter扩增仅见于原发性肿瘤。20 q13-qter扩增子存在于转移性肿瘤中。在手术后一年内发生转移的原发性肿瘤中，与在此期间没有转移的肿瘤相比，遗传改变的数量显着更高。荧光原位杂交与着丝粒和基因座特异性探针被应用于验证CGH结果的一个子集的肿瘤。FISH和CGH数据的比较给出了良好的相关性。黑色素瘤的侵袭性行为与多种遗传改变的积累有关。原发灶和转移灶的染色体区域不同，可能代表了鉴别乳腺癌相关染色体改变的潜在靶点。(C)2001 Wiley-Liss，Inc.
Characteristic genetic changes underlying the metastatic progression of malignant melanoma is incompletely understood. The goal of our study was to explore specific chromosomal alterations associated with the aggressive behavior of this neoplasm. Comparative genomic hybridization was performed to screen and compare genomic imbalances present in primary and metastatic melanomas. Sixteen primary and 12 metastatic specimens were analyzed. We found that the pattern of chromosomal aberrations is similar in the two subgroups; however, alterations present only in primary and/or metastatic tumors were also discovered. The mean number of genetic changes was 6.3 (range 1-14) in primary and 7.8 (range 1-16) in metastatic lesions. Frequent losses involved 9p and 10q, Whereas gains most often occurred at 1q, 6p, 7q, and 8q. Distinct, high-level amplifications were mapped to 1p12-p21 and 1p22-p31 in both tumor types. Amplification of 4q12-q13.1, 7q21.3-qter and 8q23-qter were detected only in primary tumors. The 20q13-qter amplicon was present in a metastatic tumor. The number of genetic alterations were significantly higher in primary tumors which developed metastases within one year after the surgery compared to tumors without metastasis during this time period. Fluorescence in situ hybridization with centromeric and locus-specific probes was applied to validate CGH results on a subset of tumors. Comparison of FISH and CGH data gave good correlation. The aggressive behavior of melanoma is associated with accumulation of multiple genetic alterations. Chromosome regions, which differ in the primary and metastatic lesions, may represent potential targets to identify metastases-related chromosomal alterations. (C) 2001 Wiley-Liss, Inc.