Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach
Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach
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DOI：
10.1182/blood-2012-07-443606
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发表时间：
2013-04-18
期刊：
影响因子：
20.3
通讯作者：
Fonseca, Rafael
中科院分区：
文献类型：
--
作者：
Baker, Angela;Braggio, Esteban;Fonseca, Rafael
流行病学数据表明，非洲裔美国人（AA）被诊断为多发性骨髓瘤（MM）的可能性是欧洲裔美国人（EA）的两倍。在这里，我们分析了一组来自AA和EA MM患者的细胞遗传学和基因组数据。我们比较了来自3项研究的115例AA患者和来自东部肿瘤协作组（ECOG）研究E4 A03和E9487的353例EA患者的一系列数据中IgH易位的频率。我们还询问了45例AA和196例EA MM患者的肿瘤，以了解与不良结局相关的体细胞拷贝数异常。此外，研究了35例AA和178例EA患者与高危疾病相关的转录谱。总体而言，基于该队列，遗传特征相似，除了AA患者中IgH易位的频率显著较低（40% vs 52%; P = 0.032）。经多次检测校正后，体细胞拷贝数畸变的频率差异不显著。基于基因表达谱的高风险疾病的频率也没有显着差异。我们的研究首次全面比较了AA和EA患者MM肿瘤中分子改变的频率和分布。ECOG E4 A03在ClinicalTrials.gov注册，编号NCT 00098475。ECOG E9487是ECOG研究E9486的伴随验证集，已在美国国立卫生研究院国家癌症研究所临床试验（PDQ）注册，编号EST-9486。
Epidemiological data have suggested that African American (AA) persons are twice as likely to be diagnosed with multiple myeloma (MM) compared with European American (EA) persons. Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from 3 studies and 353 EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs 52%; P = .032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based on gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. ECOG E4A03 is registered with ClinicalTrials.gov, number NCT00098475. ECOG E9487 is a companion validation set to the ECOG study E9486 and is registered with the National Institutes of Health, National Cancer Institute, Clinical Trials (PDQ), number EST-9486.