Recurrent mutations of NOTCH genes in follicular lymphoma identify a distinctive subset of tumours
Recurrent mutations of NOTCH genes in follicular lymphoma identify a distinctive subset of tumours
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DOI：
10.1002/path.4428
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发表时间：
2014-11-01
影响因子：
7.3
通讯作者：
Campo, Elias
中科院分区：
文献类型：
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作者：
Karube, Kennosuke;Martinez, Daniel;Campo, Elias
滤泡性淋巴瘤是最常见的恶性淋巴瘤之一。t（14;18）（q32;q21）易位在约80%的病例中被发现，并且在淋巴瘤发生中起重要作用。然而，参与这种淋巴瘤的发展和转化的分子机制尚未完全了解。最近在几种B细胞淋巴肿瘤中报道了NOTCH 1或NOTCH 2的功能获得性突变，但这些突变在FL中的作用尚不清楚。在这项研究中，我们调查了这些基因的突变状态在112个FL。在5例和2例病例中分别发现了NOTCH 1和NOTCH 2突变（共7/112，6.3%）。预测PEST结构域中截短蛋白的所有突变与其他B细胞淋巴样肿瘤中鉴定的突变相同。NOTCH突变FL病例的特征是t（14;18）频率较低（14%对69%，p = 0.01），脾脏受累发生率较高（71%对25%，p = 0.02）和女性占优势（100%对55%，p = 0.04）。在NOTCH突变的FL中，弥漫性大B细胞淋巴瘤（DLBCL）成分比野生型病例更常见（57%与18%，p = 0.03）。这些结果表明，NOTCH突变是罕见的FL，但可能发生在一个子集的情况下，独特的，特征性的，临床病理学特征。版权所有（c）2014大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Follicular lymphoma (FL) is one of the most common malignant lymphomas. The t(14;18)(q32;q21) translocation is found in about 80% of cases and plays an important role in lymphomagenesis. However, the molecular mechanisms involved in the development and transformation of this lymphoma are not fully understood. Gain-of-function mutations of NOTCH1 or NOTCH2 have recently been reported in several B cell lymphoid neoplasms but the role of these mutations in FL is not known. In this study we investigated the mutational status of these genes in 112 FLs. NOTCH1 and NOTCH2 mutations were identified in five and two cases, respectively (total 7/112, 6.3%). All mutations predicted for truncated protein in the PEST domain and were identical to those identified in other B cell lymphoid neoplasms. NOTCH-mutated FL cases were characterized by lower frequency of t(14;18) (14% versus 69%, p = 0.01), higher incidence of splenic involvement (71% versus 25%, p = 0.02) and female predominance (100% versus 55%, p = 0.04). A diffuse large B cell lymphoma (DLBCL) component was more frequently identified in NOTCH-mutated FL than in wild-type cases (57% versus 18%, p = 0.03). These results indicate that NOTCH mutations are uncommon in FL but may occur in a subset of cases with distinctive, characteristic, clinicopathological features. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.