Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, including patients of African Ancestry (AA). To begin to address this gap, we evaluated whether differences exist in the genetic and transcriptomic features of 157 AA and 440 EA individuals diagnosed with CLL. We sequenced 59 putative driver genes and found an increased frequency of high-impact mutations in AA CLL, including genes of the DNA damage repair (DDR) pathway. Telomere erosion was also increased in AA CLL, amplifying the notion of increased genomic instability in AA CLL. Furthermore, we found transcription enrichment of the Tumor Necrosis Factor-alpha (TNFα) Signaling via NF-κB pathway in AA CLL compared to EA CLL, suggesting that tumor promoting inflammation plays an important role in AA CLL. In summary, these results suggest that genomic instability and NF-kB activation is more prevalent in AA CLL than EA CLL.
尽管在描述慢性淋巴细胞白血病（CLL）的基因组图谱方面已付出大量努力，但已发表的数据几乎完全来源于欧洲血统（EA）患者，少数群体（包括非洲血统[AA]患者）的代表性严重不足。为开始填补这一空白，我们评估了157名AA患者与440名EA患者在被诊断为CLL后的遗传学及转录组学特征是否存在差异。通过对59个假定驱动基因进行测序，我们发现AA CLL患者中出现高影响力突变的频率更高，其中包括DNA损伤修复（DDR）通路相关基因。AA CLL患者的端粒侵蚀现象也更显著，这进一步强化了AA CLL基因组不稳定性更高的观点。此外，与EA CLL相比，AA CLL中通过NF-κB通路传导的肿瘤坏死因子-α（TNFα）信号在转录水平上更为富集，表明促肿瘤炎症在AA CLL中起着重要作用。总而言之，这些结果表明基因组不稳定性和NF-κB激活在AA CLL中比在EA CLL中更为普遍。
Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry
肿瘤(癌症)患者之家