Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.
Department of Laboratory Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Sci Rep. 2020 Aug 31;10(1):14297. doi: 10.1038/s41598-020-71386-z.
Acute myeloid leukemia (AML) is one of the most common types of leukemia. With the recent advances in sequencing technology and the growing body of knowledge on the genetics of AML, there is increasing concern about cancer predisposing germline mutations as well as somatic mutations. As familial cases sharing germline mutations are constantly reported, germline predisposition gene mutations in patients with AML are gaining attention. We performed genomic sequencing of Korean patients diagnosed with AML to identify the prevalence and characteristics of germline predisposition mutations. Among 180 patients, germline predisposition mutations were identified in 13 patients (13/180, 7.2%, eight adults and five children). Germline mutations of BLM, BRCA1, BRCA2, CTC1, DDX41, ERCC4, ERCC6, FANCI, FANCM, PALB2, and SBDS were identified. Most of the mutations are in genes involved in DNA repair and genomic stability maintenance. Patients harboring germline mutations tended to have earlier onset of AML (p = 0.005), however, the presence of germline mutations did not showed significant association with other clinical characteristics or treatment outcome. Since each mutation was rare, further study with a larger number of cases would be needed to establish the effect of the mutations.
急性髓系白血病 (AML) 是最常见的白血病类型之一。随着测序技术的最新进展和 AML 遗传学知识的不断增加，人们越来越关注癌症易感种系突变和体细胞突变。由于不断有家族病例共享种系突变的报道，AML 患者的种系易感性基因突变受到关注。我们对诊断为 AML 的韩国患者进行了基因组测序，以确定种系易感性突变的流行率和特征。在 180 名患者中，13 名患者（13/180，7.2%，8 名成人和 5 名儿童）存在种系易感性突变。鉴定出 BLM、BRCA1、BRCA2、CTC1、DDX41、ERCC4、ERCC6、FANCI、FANCM、PALB2 和 SBDS 的种系突变。大多数突变发生在涉及 DNA 修复和基因组稳定性维持的基因中。携带种系突变的患者 AML 发病较早（p=0.005），但种系突变的存在与其他临床特征或治疗结果无显著相关性。由于每个突变都很少见，因此需要进行更多病例的进一步研究，以确定这些突变的影响。
