Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances
Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances
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DOI：
10.1182/blood-2008-02-140616
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发表时间：
2009-01-01
期刊：
影响因子：
20.3
通讯作者：
Horsman, Douglas E.
中科院分区：
文献类型：
--
作者：
Cheung, K. -John J.;Shah, Sohrab P.;Horsman, Douglas E.
与滤泡性淋巴瘤（FL）进展相关的继发性遗传事件尚未明确定义。我们将全基因组 BAC 阵列比较基因组杂交应用于 FL 的 106 个诊断活检，以表征区域基因组失衡。使用将拷贝数变化区域定义为视觉注释和基于隐马尔可夫模型的算法之间的交叉点的分析方法，我们确定了 71 个区域改变，这些改变在至少 10% 的病例中反复出现。这些大小范围约为 200 kb 至 44 Mb，影响染色体 1、5、6、7、8、10、12、17、18、19 和 22。我们还通过聚类分析证明，106 个病例中的 46.2% 可以根据 +1q、+6p/6q-、+7 或 +18 的存在进行分组。生存分析显示，71 个区域中有 21 个区域与较差的总生存期 (OS) 显着相关。在这 21 个区域中，16 个区域是使用包含国际预后指数 (IPI) 评分的多变量 Cox 模型的 OS 独立预测因子。这 16 个区域中的两个（1p36.22-p36.33 和 6q21-q24.3）也是转化风险的预测因子并且与 IPI 无关。这些预后特征可能有助于识别高风险患者作为风险适应疗法的候选者。 （血。2009；113：137-148）
The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model-based algorithm, we identified 71 regional alterations that were recurrent in at least 10% of cases. These ranged in size from approximately 200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q-, +7, or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the international prognostic index (IPI) score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies. (Blood. 2009; 113: 137-148)