Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes
Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes
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DOI：
10.1182/blood-2012-06-437624
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发表时间：
2012-12-20
期刊：
影响因子：
20.3
通讯作者：
Cesarman, Ethel
中科院分区：
文献类型：
--
作者：
Giulino-Roth, Lisa;Wang, Kai;Cesarman, Ethel
为确定儿童伯基特淋巴瘤（pBL）的遗传基础，我们对29例福尔马林固定、石蜡包埋的原发性pBL样本中的182个癌症相关基因进行了临床级别的新一代测序。90%的病例至少有一种突变或基因改变，最常见的涉及MYC和TP53。EBV阴性病例比EBV阳性病例更有可能出现多种突变（P <.0001）。我们发现了一些此前在伯基特淋巴瘤中未描述过的肿瘤相关基因的改变。17%的病例中出现了ARID1A（SWI/SNF核小体重塑复合物的一个成员）的截短突变。22%的病例中发现了MCL1通路改变，并在一个扩大的样本组中得到了证实。20%的病例中发现了其他具有临床相关性的基因组改变。我们的数据表明了MCL1和ARID1A在伯基特淋巴瘤发病机制中的作用，并证明全面的基因组分析可能会为难治性疾病确定额外的治疗选择。（《血液》2012年；120(26):5181 - 5184）
To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations (P < .0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease. (Blood. 2012; 120(26): 5181-5184)