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Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach

机译:在非洲裔美国人中发现多发性骨髓瘤的生物学:全面的基因组学方法

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摘要

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 , number . 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.
机译: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)的可能性是欧美人(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。我们在来自3个研究的115位AA患者和来自东部合作肿瘤小组(ECOG)的E4A03和E9487研究的353 EA患者的一系列数据中比较了IgH易位的频率。我们还询问了来自45名AA和196名EA MM患者的肿瘤,发现其体细胞拷贝数异常与预后不良有关。此外,调查了35名AA和178名EA患者的与高危疾病相关的转录谱。总体而言,根据该队列研究,除了AA患者中IgH易位的频率显着降低(40%vs 52%; P = .032)外,遗传特征相似。多次测试校正后,体细胞拷贝数畸变的频率差异不明显。基于基因表达谱分析的高危疾病发生频率也没有显着差异。我们的研究代表了AA和EA患者之间MM肿瘤分子改变的频率和分布的首次全面比较。 ECOG E4A03已注册,编号。 ECOG E9487是ECOG研究E9486的伴随验证集,已在美国国立卫生研究院,美国国家癌症研究所临床试验(PDQ)注册,编号EST-9486。

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