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首页> 外文期刊>International journal of immunogenetics >HLA‐B gene somatic insertion/deletion mutations in patients with acute myelogenous leukaemia
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HLA‐B gene somatic insertion/deletion mutations in patients with acute myelogenous leukaemia

机译：HLA-B基因体细胞插入/缺失突变患者急性髓性白血病

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Abstract Loss of heterozygosity is considered to be the most common type of tumour‐specific somatic mutation of the human leucocyte antigens (HLA) genes in patients with haematological malignancies. Nevertheless, subtle DNA sequence changes, namely short insertions/deletions, may also abolish the expression of HLA molecules and interfere with routine HLA typing. Two male patients with acute myelogenous leukaemia (AML) were indicated for the search of a suitable donor for allogeneic haematopoietic stem cell transplantation (aHSCT). The patients and their relatives were initially HLA typed by serological and DNA techniques at a low‐resolution level. The HLA high‐resolution (HR) type was obtained by means of sequencing‐based typing (SBT). In both cases, anomalous frameshifts in the sequence were observed in the HLA‐B gene, namely in exon 3 (Case 1, heterozygous deletion of two bases) and exon 4 (Case 2, heterozygous insertion of two bases). In the second case, the insertion variant was associated with a loss of HLA‐B8 expression. To reveal whether these sequence patterns may be caused by somatic mutations in the malignant cells, blood sample in remission (Case 1) and buccal swab sample (Case 2) were collected from the patients. In an important manner, the SBT in these germline samples revealed common HLA‐B*07:02,*15:01 (Case 1) and HLA‐B*08:01,*35:02 (Case 2) types with no evidence for the sequence alteration observed in the initial samples. In conclusion, the insertion/deletion sequence variants of the HLA‐B gene in two patients were limited to the initial blood samples with a substantial proportion of AML cells and thus may be attributed to the somatic mutation in the malignant cells. HLA somatic mutations should be taken into account in patients with haematological malignancies to prevent HLA mistyping and inappropriate selection of an aHSCT donor.
机译：摘要杂合性的损失被认为是患有血液恶性肿瘤患者人白细胞抗原（HLA）基因的最常见的肿瘤特异性体细胞突变。然而，微妙的DNA序列变化，即插入/缺失短，也可以消除HLA分子的表达并干扰常规HLA键入。两种患有急性髓性白血病（AML）的男性患者被指示用于搜索同种异体血液干细胞移植（AHSCT）的合适供体。患者及其亲属最初是在低分辨率水平下被血清学和DNA技术键入的HLA。通过基于测序的键入（SBT）获得HLA高分辨率（HR）型。在这两种情况下，在HLA-B基因中观察到序列中的异常架构，即在外显子3（壳体1，两种碱的杂合缺失）和外显子4（壳体2，两个碱的杂合插入）。在第二种情况下，插入变体与HLA-B8表达的损失相关。为了揭示这些序列模式是否可能是由恶性细胞中的体细胞突变引起的，从患者中收集缓解（壳体1）和颊拭子样品（壳体2）中的血液样品。以一种重要的方式，这些种系样品中的SBT显示常见的HLA-B * 07：02，* 15：01（病例1）和HLA-B * 08：01，* 35：02（案例2）类型，没有证据对于在初始样品中观察到的序列改变。总之，两个患者HLA-B基因的插入/缺失序列变体仅限于具有大量比例的AML细胞的初始血液样本，因此可以归因于恶性细胞中的体细胞突变。 HLA体细胞突变应考虑到血液恶性肿瘤的患者中，以预防HLA误操作，不恰当地选择AHSCT捐赠者。

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