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Blood:二代测序揭示N-糖基化位点对滤泡性淋巴瘤发生发展的重要作用

2020-01-14 QQY MedSci原创

中心点:N-糖基化位点可在疾病早期即已获得,并在肿瘤进展过程中持续存在,即使进行了治疗。在进展过程中,N-糖基化位点-阴性亚克隆的缺乏及丢失表明阳性克隆具有扩增优势。摘要:滤泡性淋巴瘤B细胞免疫球蛋白可变区域基因经过了连续的体细胞超突变(SHM),形成异种肿瘤细胞群。SHM在V-区引入了编码N-糖基化位点天冬酰胺-X-丝氨酸/苏氨酸(N-gly位点)的DNA序列,该现象很少发生于正常B细胞。与组织

中心点:

N-糖基化位点可在疾病早期即已获得,并在肿瘤进展过程中持续存在,即使进行了治疗。

在进展过程中,N-糖基化位点-阴性亚克隆的缺乏及丢失表明阳性克隆具有扩增优势。

摘要:

滤泡性淋巴瘤B细胞免疫球蛋白可变区域基因经过了连续的体细胞超突变(SHM),形成异种肿瘤细胞群。SHM在V-区引入了编码N-糖基化位点天冬酰胺-X-丝氨酸/苏氨酸(N-gly位点)的DNA序列,该现象很少发生于正常B细胞。与组织巨噬细胞表达的钙依赖性凝集素结合后,独特的附着的寡核苷酸激活B细胞受体信号通路。这种新的相互作用对肿瘤的生长和生存似乎至关重要。

为了阐明在SHM过程中N-gly位点存在和丢失的重要性,研究人员通过二代测序跟踪了不同组患者肿瘤进化和进展过程中的位点行为。根据亚克隆之间的SHM相似度及其与胚系序列的异质性,通过谱系树来展示亚克隆的层次结构。

研究人员发现在确诊、进展和转化过程中,96%以上的亚克隆具有N-gly位点的保守性。罕见的N-gly阴性亚克隆在连续事件中丢失或可忽略,而N-gly阳性亚克隆则可以在解剖学位点之间迁移。

进行中的N-gly位点SHM导致了在疾病事件中具有不同氨基酸组成的亚克隆,但产生的绝大多数DNA序列仍能编码N-gly位点。虽然随着疾病的进展,基因组的复杂性不断变化,但只有N-gly阳性亚克隆获得选择和扩增,证明肿瘤细胞依赖于N-gly位点。在最早确诊的淋巴瘤细胞中发现了N-gly位点,表明N-gly位点突变是一个早期稳定发生的致病事件。靶向推测的甘露糖-整合素相互作用或可提供治疗选择。

原始出处:

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    2020-01-16 lfyang
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