RADIATION-ASSOCIATED BREAST TUMORS DISPLAY A DISTINCT GENE EXPRESSION PROFILE

RADIATION-ASSOCIATED BREAST TUMORS DISPLAY A DISTINCT GENE EXPRESSION PROFILE
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DOI:
10.1016/j.ijrobp.2009.09.004
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发表时间:
2010-02-01
影响因子:
7
通讯作者:
Van't Veer, Laura J.
Van't Veer, Laura J.
中科院分区:
医学1区
文献类型:
--
作者:
Broeks, Annegien;Braaf, Linde M.;Van't Veer, Laura J.

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目的:接受霍奇金淋巴瘤放疗的妇女患乳腺癌的风险大大增加。这些患者中大约90%的乳腺癌可归因于放射治疗,因此这些序列对于确定致癌过程中是否存在与放射相关的常见原因非常有用。方法和材料:在本研究中,我们使用基因表达谱技术来评估辐射相关乳腺肿瘤中基因表达的变化,并与一组同龄未暴露于辐射的女性乳腺肿瘤进行比较。从22例霍奇金淋巴瘤(BfHL)后发展为乳腺癌的患者和20例对照乳腺肿瘤的新鲜冷冻组织样本中获得RNA。结果:无监督的分层聚类数据导致辐射相关肿瘤的聚类与对照肿瘤分离(p < 0.001)。使用监督类预测工具,确定了198个探针中最接近的质心分类器。BfHL肿瘤通常属于乳腺基底肿瘤亚型,它们表现出染色体不稳定性和增殖标志物Ki-67的高表达。结论:这些结果表明,辐射相关肿瘤在表达谱上不同于其他乳腺肿瘤,它们主要是一种特定的原因,其特点是高增殖和更具侵袭性的肿瘤类型。(C) 2010爱思唯尔公司
Purpose: 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.Methods and Materials: 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.Results: 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.Conclusion: 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. (C) 2010 Elsevier Inc.