文章：

非裔美国人 vs. 欧裔美国人多发性骨髓瘤患者临床差异模式的分子基础

Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients

原文发布日期：2019-02-04

DOI: 10.1038/s41408-019-0177-9

类型: Article

开放获取: 是

英文摘要：

Caucasian Americans (CA) compared with African Americans (AA) have a twofold increased incidence of multiple myeloma (MM) and have an earlier age of diagnosis. However, there is sparse information regarding underlying biological differences across racial/ethnic groups. We characterized genetic alterations using a targeted next-generation sequencing assay called myTYPE, developed at MSKCC, allowing capture of somatic mutations, IgH translocations, gains/losses, and hyperdiploidy. Samples were obtained from the NIH Plasma Cell Dyscrasia Racial Disparity Cohort. In total, 68 patient samples were successfully sequenced and manually curated based on well-established databases. Of the 68 patient samples (47 CA, 21 AA), 84% had at least one type of genomic alteration. Importantly, the IgH translocation, t(11;14), was observed more frequently in the AA group (0 vs. 29%, p = 0.001). Known oncogenic somatic non-synonymous mutations were found in 18 genes and indels in 2 genes. KRAS mutations were the most common mutation found in 16% of patients followed by NRAS and BRAF mutations. TP53 somatic mutations appeared to be more common in CA but lacked significance. This proof-of-principle study indicates the presence of varying underlying tumor biology between racial groups and supports the need of future prospective trials to capture these molecular characteristics.

摘要翻译： 

与非洲裔美国人相比，高加索裔美国人多发性骨髓瘤的发病率高出两倍，且诊断年龄更早。然而，关于不同种族/民族群体间潜在生物学差异的信息甚少。我们采用MSKCC研发的名为myTYPE的靶向新一代测序技术对基因改变进行表征，该技术可捕获体细胞突变、IgH易位、增益/缺失及超二倍体。样本来源于NIH浆细胞疾病种族差异队列。总计68例患者样本成功完成测序，并依据权威数据库进行人工校正。在68例患者样本中，84%存在至少一种基因组改变。值得注意的是，IgH易位t(11;14)在非裔组中出现频率更高。在18个基因中发现已知致癌性体细胞非同义突变，2个基因存在插入/缺失突变。KRAS突变是最常见的突变，其次是NRAS和BRAF突变。TP53体细胞突变在高加索裔组中似乎更常见，但未达显著差异。这项原理验证研究表明不同种族群体间存在差异性的潜在肿瘤生物学特征，支持未来开展前瞻性试验以获取这些分子特征的必要性。

原文链接：

Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients