Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.
Leukemia. 2012 Jul;26(7):1602-7. doi: 10.1038/leu.2011.333. Epub 2011 Nov 18.
Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.
急性淋巴细胞白血病（ALL）是儿童中最常见的恶性疾病，通常与数量染色体异常、融合基因或小的焦点缺失相关，这些被认为是白血病发生的重要发病事件。在儿童 ALL 中也已经报道了突变，如单核苷酸变化，但这些仅通过对少数候选基因进行测序进行了研究。在此，我们报告了首例对携带 ETV6/RUNX1（TEL/AML1）融合基因（最常见的遗传亚型）的两例儿科 ALL 及其相应正常样本进行全外显子组无偏测序的结果。总共鉴定出 14 个体细胞突变，每个 ALL 中有四个和七个导致蛋白质改变的核苷酸取代。12 个突变（86%）发生在以前在其他类型癌症中描述为突变的基因中，但在扩展的 29 例 ETV6/RUNX1 阳性 ALL 中均未发现复发。单核苷酸突变的数量与通过单核苷酸多态性阵列检测到的拷贝数改变数量相似。尽管突变的真正发病意义尚待未来的功能评估，但本研究首次提供了 t(12;21)阳性儿童 ALL 遗传水平突变负担的估计。
