Wang Chunjie, Iakovlev Vladimir V, Wong Vietty, Leung Stephanie, Warren Keisha, Iakovleva Gaiane, Arneson Nona C R, Pintilie Melania, Miller Naomi, Youngson Bruce, McCready David R, Done Susan J
Division of Applied Medical Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON, Canada.
Genes Chromosomes Cancer. 2009 Dec;48(12):1091-101. doi: 10.1002/gcc.20711.
Metastatic potential of breast cancer may be associated with specific genomic alterations and the earliest metastases are likely to be found in the sentinel lymph nodes (SLN). Using array comparative genomic hybridization (aCGH), we compared the genomes of primary breast invasive duct carcinomas (IDCs), their sentinel and more distal lymph node metastases, and IDCs without nodal metastasis. Thirty-three samples from 22 patients with IDC were subjected to aCGH: 8 IDC samples from patients without lymph node metastasis, 11 IDCs associated with SLN metastases out of which 7 had paired samples of metastases, and 14 samples of lymph node metastases out of which 8 were sentinel-distal pairs from 4 patients. aCGH data were analyzed by correlation of genomic profiles, cluster analysis, segmentation, and peak identification. Quantitative real-time PCR was used for data validation. We observed high genomic similarity between primary tumors and their nodal metastases as well as between metastases to the sentinel and distal lymph nodes. Several recurrent alterations were detected preferentially in IDC associated with SLN metastases compared to IDCs without metastasis. Amplification within the 17q24.1-24.2(59.96-62.76 Mb) region was associated with presence of sentinel or distal lymph node metastases; larger tumor size and higher histological grade. In our samples, there were genomic events associated with metastatic progression, which could be detected in both primary tumors and LN metastases. Gain on 17q24.1-24.2 is a candidate region for further testing as a predictor of nodal metastasis.
乳腺癌的转移潜能可能与特定的基因组改变有关，最早的转移灶可能出现在前哨淋巴结（SLN）中。我们使用阵列比较基因组杂交（aCGH）技术，比较了原发性乳腺浸润性导管癌（IDC）、其前哨淋巴结及更远端淋巴结转移灶以及无淋巴结转移的IDC的基因组。对22例IDC患者的33个样本进行了aCGH检测：8个来自无淋巴结转移患者的IDC样本，11个与SLN转移相关的IDC样本（其中7个有配对的转移灶样本），以及14个淋巴结转移样本（其中8个是来自4例患者的前哨淋巴结-远端淋巴结配对样本）。通过基因组图谱相关性分析、聚类分析、分段分析和峰值识别对aCGH数据进行分析。采用定量实时PCR进行数据验证。我们观察到原发性肿瘤与其淋巴结转移灶之间以及前哨淋巴结和远端淋巴结转移灶之间具有高度的基因组相似性。与无转移的IDC相比，在与SLN转移相关的IDC中优先检测到几种复发性改变。17q24.1-24.2（59.96-62.76 Mb）区域内的扩增与前哨或远端淋巴结转移的存在、更大的肿瘤大小和更高的组织学分级相关。在我们的样本中，存在与转移进展相关的基因组事件，在原发性肿瘤和淋巴结转移灶中均可检测到。17q24.1-24.2区域的扩增是作为淋巴结转移预测指标进一步检测的候选区域。
