通过阵列比较基因组杂交分析揭示的1号、8号和17号染色体上卵巢癌的基因组标记。

Genomic markers for ovarian cancer at chromosomes 1, 8 and 17 revealed by array CGH analysis.

作者信息

Dimova Ivanka, Orsetti Beatrice, Negre Vincent, Rouge Carole, Ursule Liza, Lasorsa Laurence, Dimitrov Rumen, Doganov Nikolai, Toncheva Draga, Theillet Charlles

机构信息

Department of Medical Genetics, Medical University, Sofia, Bulgaria.

出版信息

Tumori. 2009 May-Jun;95(3):357-66. doi: 10.1177/030089160909500315.

DOI:10.1177/030089160909500315

PMID:19688977

Abstract

AIMS AND BACKGROUND

The literature data show that the most frequently affected chromosomes in ovarian carcinogenesis are 1, 8 and 17. In the present study we aimed to define more precisely at a high resolution the genomic imbalances of these chromosomes in ovarian cancer and to determine genomic markers separating tumors of different histological types and stages.

METHODS

Array comparative genomic hybridization (CGH) with a resolution of approximately 0.8 Mb was applied in 28 primary ovarian tumors. We identified regions of highly frequent gains or losses (affecting more than 40% of ovarian cancers) and determined sites showing alterations of elevated amplitude (amplifications or homozygous deletions). Doing this we also identified at least two adjacent changed clones.

RESULTS

We determined anomalies strongly associated with the disease such as deletions at 8p21-23, 17p12-13, 1p35-36 or amplifications at 1q23, 17q12, 17q23.2, 8q13.2, 8q24. We defined more precisely the gains in 17q12-q24, finding as strong candidates for ovarian tumorigenesis the genes LASP1 (17q12), TGF11 (17q21.32), MUL (17q23.2), TBX2 (17q23.2), AXIN2 (17q24.3) and GRB2 (17q25.1). Of particular note was gain of 8q13.2, which occurred at a high frequency in ovarian cancer, especially in serous and late-stage tumors. We found that gains of 1q32-1q43, 8p11-p12, 8q11.23, 8q13.2, and 8q24.21-8q24.22 and losses of 1p36.21, 8p23.1-8p21.1 and 8q21.2 were associated with serous histology, whereas losses of 1q23 and 1q32-43 and gains of 17q11.2-12 and 17q25 were associated with mucinous histology. Gains of 1q23, 8q24, 17q23.2, 17q24.2 and losses of 1p35-36, 8p, 17p, and 17q were specific for late-stage ovarian cancers.

CONCLUSIONS

Our study has identified potential genomic markers of interest on chromosomes 1, 8 and 17 in ovarian cancer. Tumors showed a wide variety in the patterns of alteration, suggesting that alternative mechanisms of genomic instability may play a role in this tumor type.

摘要

目的与背景

文献数据表明，卵巢癌发生过程中最常受累的染色体是1号、8号和17号染色体。在本研究中，我们旨在以高分辨率更精确地界定卵巢癌中这些染色体的基因组失衡情况，并确定区分不同组织学类型和分期肿瘤的基因组标志物。

方法

对28例原发性卵巢肿瘤应用分辨率约为0.8 Mb的阵列比较基因组杂交（CGH）技术。我们确定了高频获得或缺失区域（影响超过40%的卵巢癌），并确定了显示振幅改变的位点（扩增或纯合缺失）。在此过程中，我们还确定了至少两个相邻的变化克隆。

结果

我们确定了与该疾病密切相关的异常情况，如8p21 - 23、17p12 - 13、1p35 - 36区域的缺失或1q23、17q12、17q23.2、8q13.2、8q24区域的扩增。我们更精确地界定了17q12 - q24区域的获得情况，发现LASP1（17q12）、TGF11（17q21.32）、MUL（17q23.2）、TBX2（17q23.2）、AXIN2（17q24.3）和GRB2（17q25.1）基因是卵巢肿瘤发生的有力候选基因。特别值得注意的是8q13.2区域的获得，其在卵巢癌中高频出现，尤其是在浆液性和晚期肿瘤中。我们发现1q32 - 1q43、8p11 - p12、8q11.23、8q13.2和8q24.21 - 8q24.22区域的获得以及1p36.21、8p23.1 - 8p21.1和8q21.2区域的缺失与浆液性组织学相关，而1q23和1q32 - 43区域的缺失以及17q11.2 - 12和17q25区域的获得与黏液性组织学相关。1q23、8q24、17q23.2、17q24.2区域的获得以及1p35 - 36、8p、17p和17q区域的缺失是晚期卵巢癌的特征。