Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins University Kimmel Cancer Center, Baltimore, MD 21231, USA.
Blood. 2011 Nov 24;118(22):5914-7. doi: 10.1182/blood-2011-05-356204. Epub 2011 Oct 11.
To further our understanding of the genetic basis of acute myelogenous leukemia (AML), we determined the coding exon sequences of ∼ 18 000 protein-encoding genes in 8 patients with secondary AML. Here we report the discovery of novel somatic mutations in the transcriptional corepressor gene BCORL1 that is located on the X-chromosome. Analysis of BCORL1 in an unselected cohort of 173 AML patients identified a total of 10 mutated cases (6%) with BCORL1 mutations, whereas analysis of 19 AML cell lines uncovered 4 (21%) BCORL1 mutated cell lines. The majority (87%) of the mutations in BCORL1 were predicted to inactivate the gene product as a result of nonsense mutations, splice site mutation, or out-of-frame insertions or deletions. These results indicate that BCORL1 by genetic criteria is a novel candidate tumor suppressor gene, joining the growing list of genes recurrently mutated in AML.
为了进一步了解急性髓系白血病（AML）的遗传基础，我们在 8 名继发性 AML 患者中测定了约 18000 个编码蛋白基因的编码外显子序列。在此，我们报告了在位于 X 染色体上的转录共抑制因子基因 BCORL1 中发现的新的体细胞突变。在对 173 例 AML 患者的未选择队列进行分析时，共发现了 10 例（6%）BCORL1 突变病例，而在对 19 个 AML 细胞系进行分析时，发现了 4 例（21%）BCORL1 突变的细胞系。BCORL1 中的大多数（87%）突变被预测由于无意义突变、剪接位点突变或移码插入或缺失而使基因产物失活。这些结果表明，BCORL1 通过遗传标准是一个新的候选肿瘤抑制基因，加入了在 AML 中经常发生突变的基因列表。
