Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH
Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH
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DOI：
10.1007/s10549-008-0117-z
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发表时间：
2009-08-01
影响因子：
3.8
通讯作者：
Nederlof, Petra M.
中科院分区：
文献类型：
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作者：
Joosse, Simon A.;van Beers, Erik H.;Nederlof, Petra M.
背景虽然BRCA1的新缺陷仍在被发现，但目前的乳腺癌诊断是否遗漏了许多BRCA1相关病例尚不清楚。一项能够表明BRCA1缺陷与癌症发生有关的可靠测试可以支持遗传咨询和临床管理的决策。为了寻找brca1特异性标记物并探索当前诊断策略的有效性，我们设计了一种分类方法，对其进行了验证，并检查了我们是否可以在一组最初诊断为非brca1 /2突变携带者的患者中发现brca1样乳腺肿瘤。方法基于18例brca1相关乳腺癌和32例对照乳腺癌的阵列- cgh图谱构建分类器，并在16例brca1相关乳腺癌和16例对照乳腺癌的独立组上进行验证。随后，我们将该分类器应用于48例未发现生殖系BRCA1/BRCA2突变的遗传性乳腺癌和卵巢癌（HBOC）家族患者的乳腺肿瘤。结果该分类器在验证集上的准确率为91%。在48例非brca1 /2患者中，只有2例乳腺肿瘤呈现brca1样CGH特征。在其中一个肿瘤中发现了BRCA1功能障碍的其他证据。结论我们描述了brca1相关乳腺癌的特异性染色体畸变。我们开发了一种预测brca1关联的基因测试，并表明在常规DNA诊断后，仍可以在HBOC家族中识别出brca1相关肿瘤。
Background While new defects in BRCA1 are still being found, it is unclear whether current breast cancer diagnostics misses many BRCA1-associated cases. A reliable test that is able to indicate the involvement of BRCA1 deficiency in cancer genesis could support decision making in genetic counselling and clinical management. To find BRCA1-specific markers and explore the effectiveness of the current diagnostic strategy, we designed a classification method, validated it and examined whether we could find BRCA1-like breast tumours in a group of patients initially diagnosed as non-BRCA1/2 mutation carriers. Methods A classifier was built based on array-CGH profiles of 18 BRCA1-related and 32 control breast tumours, and validated on independent sets of 16 BRCA1-related and 16 control breast carcinomas. Subsequently, we applied the classifier to 48 breast tumours of patients from Hereditary Breast and Ovarian Cancer (HBOC) families in whom no germ line BRCA1/BRCA2 mutations were identified. Results The classifier showed an accuracy of 91% when applied to the validation sets. In 48 non-BRCA1/2 patients, only two breast tumours presented a BRCA1-like CGH profile. Additional evidence for BRCA1 dysfunction was found in one of these tumours. Conclusion We here describe the specific chromosomal aberrations in BRCA1-related breast carcinomas. We developed a predictive genetic test for BRCA1-association and show that BRCA1-related tumours can still be identified in HBOC families after routine DNA diagnostics.