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揭示非裔美国人多发性骨髓瘤的生物学机制:一种综合基因组学方法。

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

机构信息

Translational Genomics Research Institute, Phoenix, AZ, USA.

出版信息

Blood. 2013 Apr 18;121(16):3147-52. doi: 10.1182/blood-2012-07-443606. Epub 2013 Feb 19.

Abstract

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.

摘要

流行病学数据表明,非裔美国人(AA)患多发性骨髓瘤(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 名 AA 患者和来自东部合作肿瘤学组(ECOG)研究 E4A03 和 E9487 的 353 名 EA 患者的一系列数据中 IgH 易位的频率。我们还研究了来自 45 名 AA 和 196 名 EA MM 患者的肿瘤是否存在与不良预后相关的体细胞拷贝数异常。此外,还研究了 35 名 AA 和 178 名 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,但 AA 患者的 IgH 易位频率明显较低(40%对 52%;P =.032)。在进行多次测试校正后,体细胞拷贝数异常的频率差异没有统计学意义。基于基因表达谱,高危疾病的频率也没有显著差异。本研究代表了首次对 AA 和 EA 患者 MM 肿瘤中分子改变的频率和分布进行全面比较。ECOG E4A03 在 ClinicalTrials.gov 注册,编号为 NCT00098475。ECOG E9487 是 ECOG 研究 E9486 的配套验证集,在国立卫生研究院、美国国立癌症研究所、临床试验(PDQ)注册,编号为 EST-9486。

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