Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.

Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.
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DOI:
10.1186/1471-2407-6-92
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发表时间:
2006-04-12
期刊:
影响因子:
3.8
通讯作者:
Noh DY
Noh DY
中科院分区:
医学2区
文献类型:
--
作者:
Han W;Han MR;Kang JJ;Bae JY;Lee JH;Bae YJ;Lee JE;Shin HJ;Hwang KT;Hwang SE;Kim SW;Noh DY

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相当比例的雌激素受体(ER)阳性乳腺癌在他莫昔芬治疗后仍会复发,这是临床实践中经常遇到的严重问题。我们试图在这种乳腺癌亚型中寻找新的预后标志物。我们对1440个人类细菌人工染色体(BAC)克隆进行了阵列比较基因组杂交(CGH),以评估28个新鲜冷冻er阳性乳腺癌组织的拷贝数变化。所有纳入的患者都接受了至少1年的他莫昔芬治疗。9例患者在诊断后5年内出现远处复发(复发组),19例患者在诊断后至少5年内无疾病生存(未复发组)。两组之间的潜在预后变量具有可比性。在无监督聚类分析中,来自每组的样本被很好地分离。所有样本中最常见的增益区域为1q32.1、17q23.3、8q24.11、17q12-q21.1和8p11.21,最常见的损失区域为6q14.1-q16.3、11q21-q24.3和13q13.2-q14.3。两组间拷贝数变化的平均频率相似。用两种不同的统计方法在复发组中更常发现的最显著的染色体改变是11p15.5-p15.4、1p36.33、11q13.1和11p11.2的缺失(校正p值<0.001)。根据淋巴结状态进行亚组分析,复发组11p15和1p36丢失较多,在淋巴结阳性患者中具有临界意义(调整p = 0.052)。我们使用BAC克隆的阵列CGH分析可以检测er阳性乳腺癌的各种基因组变化,复发组样本的DNA拷贝数变化模式明显不同于非复发组样本。
A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group). Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052). Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples.
DOI: 10.1023/a:1023025506386
发表时间: 2003-04-01
影响因子: 3.8
作者:
Albertson, DG
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DOI: 10.1093/hmg/7.5.895
发表时间: 1998-05-01
影响因子: 3.5
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DOI: 10.1093/bioinformatics/bth355
发表时间: 2004-12-12
期刊: BIOINFORMATICS
影响因子: 5.8
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DOI: 10.1007/s001220050428
发表时间: 1997-03-01
影响因子: 5.4
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通讯作者: Michelmore, RW
DOI: 10.1093/jnci/91.5.453
发表时间: 1999-03-03
期刊: JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子: --
作者:
Hilsenbeck, SG;Friedrichs, WE;Fuqua, SAW
通讯作者: Fuqua, SAW