In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin's lymphoma (NHL).
In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin's lymphoma (NHL).
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DOI：
10.1186/1471-2164-15-390
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发表时间：
2014-05-21
期刊：
影响因子：
4.4
通讯作者：
Griffiths LR
中科院分区：
文献类型：
--
作者：
Aya-Bonilla C;Camilleri E;Haupt LM;Lea R;Gandhi MK;Griffiths LR
参与肿瘤发生的细胞网络和途径的分析增加了我们对肿瘤生物学基础的致病机制的了解，并揭示了可能导致设计更好的抗癌疗法的新分子靶点。最近，使用高分辨率杂合性丢失（洛）分析，我们确定了一些潜在的肿瘤抑制基因（TSGs）的共同洛区域的情况下，患有两个最常见的形式的非霍奇金淋巴瘤（NHL），滤泡性淋巴瘤（FL）和弥漫性大B细胞淋巴瘤（DLBCL）。从这些研究中，蛋白酪氨酸磷酸酶受体J型（PTPRJ）基因的洛被确定为这些B细胞淋巴瘤的淋巴瘤发生中的常见事件。本研究旨在确定FL和DLBCL肿瘤发生中受这些TSG（包括PTPRJ）失活影响的细胞途径。通路分析方法鉴定了位于共同洛区域内的候选TSGs参与细胞通路，其可能在FL和DLBCL淋巴瘤发生中起关键作用（即，代谢途径）。这些分析还确定了PTPRJ相互作用组（即PTPN 11和B2 M）中的基因，这些基因在NHL中失活时可能在肿瘤发生中发挥重要作用。我们还检测了在有和没有PTPRJ的洛的病例中差异表达的基因，例如NFATC 3（活化T细胞的核因子，胞质，钙调神经磷酸酶依赖性3）。此外，在具有PTPRJ的洛的NHL病例中也观察到VEGF、MAPK和ERBB信号传导途径的上调，这表明导致PTPRJ失活的LOH驱动事件，除了可能通过降低或消除其去磷酸化活性诱导这些途径的组成性激活之外，还可能在失活时诱导这些途径的上调。这一发现暗示这些途径在淋巴瘤发生和FL和DLBCL的进展。本研究中获得的证据支持FL和DLBCL具有共同的致病机制。此外，它表明，PTPRJ可以在这些B细胞肿瘤的发病机制中发挥至关重要的作用，并表明PTPRJ的激活可能是一个有趣的新的化疗靶点，用于治疗这些B细胞肿瘤。本文的在线版本（doi：10.1186/1471-2164-15-390）包含补充材料，可供授权用户使用。
The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours. The online version of this article (doi: 10.1186/1471-2164-15-390) contains supplementary material, which is available to authorized users.
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影响因子：
7.8
作者：
Lampugnani, MG;Zanetti, A;Corada, M;Takahashi, T;Balconi, G;Breviario, F;Orsenigo, F;Cattelino, A;Kemler, R;Daniel, TO;Dejana, E
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Östman, A
影响因子：
2.6
作者：
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通讯作者：
Yavuz, Sinan
影响因子：
3.7
作者：
Green, Michael R.;Aya-Bonilla, Carlos;Griffiths, Lyn R.
通讯作者：
Griffiths, Lyn R.