Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):540-7. doi: 10.1016/j.ijrobp.2009.09.004.
Women who received irradiation for Hodgkin's lymphoma have a strong increased risk for developing breast cancer. Approximately 90% of the breast cancers in these patients can be attributed to their radiation treatment, rendering such series extremely useful to determine whether a common radiation-associated cause underlies the carcinogenic process.
In this study we used gene expression profiling technology to assess gene expression changes in radiation-associated breast tumors compared with a set of control breast tumors of women unexposed to radiation, diagnosed at the same age. RNA was obtained from fresh frozen tissue samples from 22 patients who developed breast cancer after Hodgkin's lymphoma (BfHL) and from 20 control breast tumors.
Unsupervised hierarchical clustering of the profile data resulted in a clustering of the radiation-associated tumors separate from the control tumors (p < 0.001). Using a supervised class prediction tool, a nearest centroid classifier of 198 probes was identified. The BfHL tumors were often of the intrinsic basal breast tumor subtype, and they showed a chromosomal instability profile and a higher expression of the proliferation marker Ki-67.
These results indicate that radiation-associated tumors are different from other breast tumors on the basis of their expression profile and that they are mainly of one specific cause that is characterized by high proliferation and a more aggressive tumor type.
接受霍奇金淋巴瘤放疗的女性罹患乳腺癌的风险显著增加。这些患者中约 90%的乳腺癌可归因于放疗，因此此类系列研究非常有助于确定是否存在共同的辐射相关因素导致了致癌过程。
在这项研究中，我们使用基因表达谱分析技术来评估与一组未接受辐射的对照组乳腺癌相比，与接受辐射相关的乳腺癌中的基因表达变化。这些对照组的乳腺癌患者年龄相同，均为在诊断时未接受过辐射。从 22 名霍奇金淋巴瘤（BfHL）后发生乳腺癌的患者的新鲜冷冻组织样本中获取 RNA，并从 20 名对照组的乳腺癌患者中获取 RNA。
对数据的无监督层次聚类导致辐射相关肿瘤与对照组肿瘤分离（p < 0.001）。使用有监督的分类预测工具，确定了 198 个探针的最近中心分类器。BfHL 肿瘤通常属于固有基底乳腺癌亚型，它们表现出染色体不稳定性特征和增殖标志物 Ki-67 的高表达。
这些结果表明，基于其表达谱，辐射相关肿瘤与其他乳腺癌不同，它们主要是由一种特定的原因引起的，其特征是高增殖和更具侵袭性的肿瘤类型。
