Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma.
Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma.
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DOI：
10.3324/haematol.2016.160192
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发表时间：
2017-10
期刊：
影响因子：
10.1
通讯作者：
Traverse-Glehen A
中科院分区：
文献类型：
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作者：
Jallades L;Baseggio L;Sujobert P;Huet S;Chabane K;Callet-Bauchu E;Verney A;Hayette S;Desvignes JP;Salgado D;Levy N;Béroud C;Felman P;Berger F;Magaud JP;Genestier L;Salles G;Traverse-Glehen A
脾脏弥漫性红髓淋巴瘤是一种惰性小B细胞淋巴瘤，在世界卫生组织2008年分类中被认为是临时实体。它与其他相关的脾B细胞淋巴瘤伴白血病或其他淋巴增生性疾病的确切关系尚未确定。我们使用配对的肿瘤和正常样本进行全外显子组测序，以探讨10例脾脏弥漫性红髓淋巴瘤的遗传景观。然后在包括42个脾弥漫性红髓淋巴瘤样本的队列中评估了109个体细胞突变的选择，并与46个脾边缘区淋巴瘤样本和8个毛细胞白血病样本中鉴定的体细胞突变进行了比较。在10/42例脾弥漫性红髓淋巴瘤（24%）中发现了BCOR（编码BCL 6辅阻遏物的基因）的复发突变或丢失-移码（n=3），无义（n=2），剪接位点（n=1）和拷贝数丢失（n=4），而在46例脾边缘区淋巴瘤（2%）中仅发现了一个移码突变。脾脏边缘区淋巴瘤中常见的突变有Inflammatory、KLF 2、TNFAIP 3和MYD 88，而在脾脏弥漫性红髓淋巴瘤中则罕见（42例中有1例KLF 2突变; 2%）或缺失（TNFAIP 3和MYD 88）。这些研究结果定义了脾脏弥漫性红髓淋巴瘤的原始遗传特征，并表明这种淋巴瘤的发病机制与脾脏边缘区淋巴瘤和毛细胞白血病不同。
Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognized as a provisional entity in the World Health Organization 2008 classification. Its precise relationship to other related splenic B-cell lymphomas with frequent leukemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of ten cases of splenic diffuse red pulp lymphoma using paired tumor and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 samples of splenic diffuse red pulp lymphoma and compared to those identified in 46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6 corepressor) – frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4) – were identified in 10/42 samples of splenic diffuse red pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 cases of splenic marginal zone lymphoma (2%). Inversely, KLF2, TNFAIP3 and MYD88, common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse red pulp lymphoma. These findings define an original genetic profile of splenic diffuse red pulp lymphoma and suggest that the mechanisms of pathogenesis of this lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell leukemia.