The genetic landscape of dural marginal zone lymphomas.
The genetic landscape of dural marginal zone lymphomas.
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DOI：
10.18632/oncotarget.9678
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发表时间：
2016-07-12
期刊：
影响因子：
--
通讯作者：
Bhagat G
中科院分区：
文献类型：
--
作者：
Ganapathi KA;Jobanputra V;Iwamoto F;Jain P;Chen J;Cascione L;Nahum O;Levy B;Xie Y;Khattar P;Hoehn D;Bertoni F;Murty VV;Pittaluga S;Jaffe ES;Alobeid B;Mansukhani MM;Bhagat G
硬脑膜是边缘区淋巴瘤（MZL）累及的罕见部位，硬脑膜MZL的生物学尚不清楚。我们对14例硬脑膜MZL进行了全基因组DNA拷贝数和靶向突变分析，以确定该实体的遗传景观。在6/9例（67%）表现出浆细胞分化的硬脑膜MZL（包括3例IgG 4+病例）中观察到TNFAIP 3突变（n=5）或缺失（n=1）导致的单等位基因和双等位基因失活。相反，激活NOTCH 2突变检测4/5（80%）硬脑膜MZL显示可变单核细胞样形态。在所有NOTCH 2突变病例中鉴定了失活TBL 1XR 1突变。还检测到KLHL 6（n=2）和MLL 2（n=2）中的复发突变。6p25.3的增加（n=2）和1p36.32的丢失（n=3）是常见的染色体不平衡，在一个病例子集中观察到这些位点的杂合性丢失（洛）。未发现涉及IGH或MALT 1基因的易位。我们的研究结果表明硬脑膜MZL和其他MZL亚型之间的遗传相似性。然而，TNFAIP 3和NOTCH 2的复发性和相互排斥的遗传改变似乎与硬脑膜MZL中不同的疾病表型相关。
The dura is a rare site of involvement by marginal zone lymphoma (MZL) and the biology of dural MZL is not well understood. We performed genome-wide DNA copy number and targeted mutational analysis of 14 dural MZL to determine the genetic landscape of this entity. Monoallelic and biallelic inactivation of TNFAIP3 by mutation (n=5) or loss (n=1) was observed in 6/9 (67%) dural MZL exhibiting plasmacytic differentiation, including 3 IgG4+ cases. In contrast, activating NOTCH2 mutations were detected in 4/5 (80%) dural MZL displaying variable monocytoid morphology. Inactivating TBL1XR1 mutations were identified in all NOTCH2 mutated cases. Recurrent mutations in KLHL6 (n=2) and MLL2 (n=2) were also detected. Gains at 6p25.3 (n=2) and losses at 1p36.32 (n=3) were common chromosomal imbalances, with loss of heterozygosity (LOH) of these loci observed in a subset of cases. Translocations involving the IGH or MALT1 genes were not identified. Our results indicate genetic similarities between dural MZL and other MZL subtypes. However, recurrent and mutually exclusive genetic alterations of TNFAIP3 and NOTCH2 appear to be associated with distinct disease phenotypes in dural MZL.
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影响因子：
20.3
作者：
Chu, Yuanyuan;Vahl, J. Christoph;Schmidt-Supprian, Marc
通讯作者：
Schmidt-Supprian, Marc
影响因子：
45.3
作者：
Tu, PH;Giannini, C;Perry, A
通讯作者：
Perry, A
DOI：
10.3324/haematol.2011.040402
发表时间：
2011-07-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Kwee, Ivo;Rancoita, Paola M. V.;Bertoni, Francesco
通讯作者：
Bertoni, Francesco
影响因子：
64.8
作者：
Compagno, Mara;Lim, Wei Keat;Grunn, Adina;Nandula, Subhadra V.;Brahmachary, Manisha;Shen, Qiong;Bertoni, Francesco;Ponzoni, Maurilio;Scandurra, Marta;Califano, Andrea;Bhagat, Govind;Chadburn, Amy;Dalla-Favera, Riccardo;Pasqualucci, Laura
通讯作者：
Pasqualucci, Laura
影响因子：
7.3
作者：
Karube, Kennosuke;Martinez, Daniel;Campo, Elias
通讯作者：
Campo, Elias