High-resolution mapping of DNA breakpoints to define true recurrences among lpsilateral breast cancers
High-resolution mapping of DNA breakpoints to define true recurrences among lpsilateral breast cancers
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DOI：
10.1093/jnci/djm266
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发表时间：
2008-01-02
影响因子：
10.3
通讯作者：
Thiery, Jean-Paul
中科院分区：
文献类型：
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作者：
Bollet, Marc A.;Servant, Nicolas;Thiery, Jean-Paul
背景 为了区分新发原发性乳腺癌和真正的复发，使用单核苷酸多态性阵列对 DNA 拷贝数改变 (CNA) 进行全基因组分析已被证明是有用的。方法对来自同一患者的 22 对原发性乳腺癌（导管癌或小叶癌）和同侧乳腺癌的全基因组图谱进行了分析。使用 CNA 和 DNA 断点信息进行分层聚类。使用 DNA 断点信息开发的部分同一性评分用于量化两个肿瘤之间的部分同一性。使用聚类方法和部分同一性评分定义的同侧乳腺癌的性质（真实复发与新原发肿瘤）与基于临床特征的评分进行比较。使用部分同一性评分和临床特征对原发性肿瘤患者和真实复发患者的无转移生存率进行比较。所有统计检验均为两侧。结果 对于 14 对样本，所有方法都同意同侧乳腺癌的性质。对于五对，临床定义与两种聚类方法均不一致。对于三对，两种聚类方法不一致，而使用 DNA 断点的聚类方法与临床定义一致。部分同一性评分证实了同侧乳腺癌的性质，这是通过 22 对中的 21 对中 DNA 断点的聚类来定义的。当根据临床和组织学特征定义肿瘤时，新原发肿瘤患者和真正复发患者的无转移生存率差异不具有统计学意义（新原发肿瘤的5年无转移生存率：76%，95%置信区间[CI] = 52%至100%，真正复发的5年无转移生存率：38%，95% CI = 17%至83%；P = .18；新原发肿瘤与真实复发，风险比率 = 2.8，95% Cl = 0.6 至 13.7），但当使用部分同一性评分定义肿瘤时，差异具有统计学意义（5 年无转移生存率：新原发肿瘤为 100%，真正复发为 29%，95% Cl = 11% 至 78%；P =.01）。 结论 在该人群中，DNA 断点信息比 CNAs 更常与临床测定一致。基于 DNA 断点计算的部分同一性评分可以在新的原发性肿瘤和真正的复发之间进行统计区分，这在预后方面可能优于临床确定。
Background To distinguish new primary breast cancers from true recurrences, pangenomic analyses of DNA copy number alterations (CNAs) using sing le-nucleotide polymorphism arrays have proven useful.Methods The pangenomic profiles of 22 pairs of primary breast carcinoma (ductal or lobular) and ipsilateral breast cancers from the same patients were analyzed. Hierarchical clustering was performed using CNAs and DNA breakpoint information. A partial identity score developed using DNA breakpoint information was used to quantify partial identities between two tumors. The nature of ipsilateral breast cancers (true recurrence vs new primary tumor) as defined using the clustering methods and the partial identity score was compared with that based on clinical characteristics. Metastasis-free survival was compared among patients with primary tumors and true recurrences as defined using the partial identity score and by clinical characteristics. All statistical tests were two-sided.Results All methods agreed on the nature of ipsilateral breast cancers for 14 pairs of samples. For five pairs, the clinical definition disagreed with both clustering methods. For three pairs, the two clustering methods were discordant and the one using DNA breakpoints agreed with the clinical definition. The partial identity score confirmed the nature of ipsilateral breast cancers as defined by clustering of DNA breakpoints in 21 of 22 pairs. The difference in metastasis-free survival of patients with new primary tumors and those with true recurrences was not statistically significant when tumors were defined based on clinical and histologic characteristics (5-year metastasis-free survival: 76%, 95% confidence interval [CI] = 52% to 100% for new primary tumors and 38%, 95% Cl = 17% to 83% for true recurrences; P =.18; new primary tumor vs true recurrence, hazard ratio = 2.8, 95% Cl = 0.6 to 13.7), but the difference was statistically significant when tumors were defined using the partial identity score (5-year metastasis-free survival: 100% for new primary tumors and 29%, 95% Cl = 11 % to 78% for true recurrences; P =.01).Conclusions DNA breakpoint information more often agreed with the clinical determination than CNAs in this population. The partial identity score, which was calculated based on DNA breakpoints, allows statistical discrimination between new primary tumors and true recurrences that could outperform the clinical determination in terms of prognosis.