Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0936, USA,
Adv Exp Med Biol. 2013;792:47-86. doi: 10.1007/978-1-4614-8051-8_3.
Approximately 80 % of chronic lymphocytic leukemia (CLL) carries somatically acquired genomic copy number aberrations (aCNAs). These include gains of entire chromosomes (trisomy 12) and recurrent genomic losses, including interstitial deletions of various lengths at 13q14, 11q, and of more uniform length at 17p. In addition, approximately 10-15 second-tier aCNAs, with frequencies of 1-5 %, have been identified. In this chapter, we will discuss the biology and clinical significance of these CLL-associated aCNAs in detail and also discuss generic aspects of aCNAs relevant to all cancer cells. The hypothesis is advanced that most if not all aCNAs in CLL deregulate multiple target genes as a consequence of aCNA-associated gene mutations and through stable deregulation of gene expression. The concept of elevated genomic complexity (multiple aCNAs per CLL case) is reinforced as one of the strongest biological traits associated with aggressive CLL with short survival. Further, all inherited polymorphic copy number variations as detected through SNP 6.0 array profiling of T-cell-derived DNA of 255 CLL patients are listed to allow the reader a more critical appraisal of the somatic status of CLL-associated aCNAs as reported in the literature. Finally, given that aCNAs and gene mutations coexist in many CLL cells, we stress the importance of understanding in detail the relative biological and clinical roles each mutation type serves in individual CLL patients; this is a research area in need of more in-depth investigation.
大约 80%的慢性淋巴细胞白血病（CLL）携带体细胞获得的基因组拷贝数异常（aCNAs）。这些异常包括整条染色体的增益（12 三体）和反复出现的基因组缺失，包括 13q14、11q 上不同长度的染色体间缺失以及 17p 上更均匀长度的缺失。此外，还鉴定出了大约 10-15 种次要的 aCNAs，其频率为 1-5%。在这一章中，我们将详细讨论这些与 CLL 相关的 aCNAs 的生物学和临床意义，并讨论与所有癌细胞相关的 aCNAs 的一般方面。提出的假设是，CLL 中的大多数（如果不是全部）aCNAs 通过 aCNA 相关基因突变和基因表达的稳定失调来调节多个靶基因。升高的基因组复杂性（每个 CLL 病例中有多个 aCNAs）的概念被强化为与短生存时间的侵袭性 CLL 相关的最强生物学特征之一。此外，通过对 255 例 CLL 患者的 T 细胞衍生 DNA 进行 SNP 6.0 芯片分析检测到的所有遗传多态性拷贝数变异也被列出，以便读者更批判性地评估文献中报道的与 CLL 相关的 aCNAs 的体细胞状态。最后，鉴于 aCNAs 和基因突变在许多 CLL 细胞中共存，我们强调详细了解每种突变类型在个体 CLL 患者中相对生物学和临床作用的重要性；这是一个需要更深入研究的研究领域。
