Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma
Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma
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DOI：
10.1182/blood-2011-03-341560
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发表时间：
2011-07-21
期刊：
影响因子：
20.3
通讯作者：
Aaltonen, Lauri A.
中科院分区：
文献类型：
--
作者：
Saarinen, Silva;Aavikko, Mervi;Aaltonen, Lauri A.
霍奇金淋巴瘤在某些家族中的强聚集性早已被公认。然而，家族性霍奇金淋巴瘤背景中的遗传因素在很大程度上是未知的。我们研究了一个家族的4个堂兄弟与罕见亚型的疾病，结节淋巴细胞为主的霍奇金淋巴瘤。我们应用外显子组测序和全基因组连锁分析，该家庭，并确定了核蛋白，共济失调毛细血管扩张症基因座（NPAT）基因的截断种系突变，在家庭中分离。我们还研究了来自其他霍奇金淋巴瘤患者的大量样本，在几个病例中发现了导致丝氨酸724缺失的种系变异，这表明该疾病的风险升高（比值比= 4.11; P = 0.018）。NPAT是迄今为止第一个与结节性淋巴细胞为主的霍奇金淋巴瘤易感性有关的基因。（血。2011;118（3）：493-498）
A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma. We applied exome sequencing together with genome-wide linkage analysis to this family and identified a truncating germline mutation in nuclear protein, ataxia-telangiectasia locus (NPAT) gene, which segregated in the family. We also studied a large number of samples from other patients with Hodgkin lymphoma, and a germline variation leading to the deletion of serine 724 was found in several cases suggesting an elevated risk for the disease (odds ratio = 4.11; P = .018). NPAT is thus far the first gene implicated in nodular lymphocyte predominant Hodgkin lymphoma predisposition. (Blood. 2011;118(3):493-498)