慢性淋巴细胞白血病 (CLL) 的特点是多拷贝数改变 (CNA) 和体细胞突变，这些突变对于疾病预后、风险分层和治疗耐药机制至关重要。荧光原位杂交 (FISH) 组合广泛应用于临床应用，作为筛查 CLL 预后染色体异常的金标准。 DNA 测序是识别 CNA 的另一种方法，但不是临床 CNA 筛查的既定方法。我们对 509 名患有 CLL 或单克隆 B 细胞淋巴细胞增多症 (MBL)（CLL 的前体）的个体进行了 DNA 测序，使用了包含 59 个 CLL 中反复突变基因的靶向测序组以及跨受临床相关 CNA 影响的区域的其他扩增子 [即 del( 17p)、del(11q)、del(13q) 和 12 三体]。我们使用PatternCNV算法调用CNA，并将通过靶向测序调用临床相关CNA的一致性与FISH进行比较。我们发现与 FISH 相比，通过测序调用 CNA 的准确性更高。以FISH为金标准，在临床相关CNA中，靶向测序的特异性>95%，敏感性>86%，阳性预测值>90%，阴性预测值>84%。使用靶向测序，我们还能够识别其他常见的 CLL 相关 CNA，包括 del(6q)、del(14q) 和增益 8q，以及复杂核型（定义为存在 3 种或更多染色体异常） 26名患者。在可对存储的 DNA 样本进行的单一且经济高效的检测中，靶向测序可以同时检测 CNA、体细胞突变和复杂核型，这些都是 CLL 的重要预后特征。

Chronic lymphocytic leukemia (CLL) is characterized by multiple copy number alterations (CNAs) and somatic mutations that are central to disease prognosis, risk stratification, and mechanisms of therapy resistance. Fluorescence in situ hybridization (FISH) panels are widely used in clinical applications as the gold standard for screening prognostic chromosomal abnormalities in CLL. DNA sequencing is an alternative approach to identifying CNAs but is not an established method for clinical CNA screening. We sequenced DNA from 509 individuals with CLL or monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, using a targeted sequencing panel of 59 recurrently mutated genes in CLL and additional amplicons across regions affected by clinically relevant CNAs [i.e., del(17p), del(11q), del(13q), and trisomy 12]. We used the PatternCNV algorithm to call CNA and compared the concordance of calling clinically relevant CNAs by targeted sequencing to that of FISH. We found a high accuracy of calling CNAs via sequencing compared to FISH. With FISH as the gold standard, the specificity of targeted sequencing was >95%, sensitivity was >86%, positive predictive value was >90%, and negative predictive value was >84% across the clinically relevant CNAs. Using targeted sequencing, we were also able to identify other common CLL-associated CNAs, including del(6q), del(14q), and gain 8q, as well as complex karyotype, defined as the presence of 3 or more chromosomal abnormalities, in 26 patients. In a single and cost-effective assay that can be performed on stored DNA samples, targeted sequencing can simultaneously detect CNAs, somatic mutations, and complex karyotypes, which are all important prognostic features in CLL.