Mutations of the PIK3CA gene in diffuse large B cell lymphoma.
Mutations of the PIK3CA gene in diffuse large B cell lymphoma.
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DOI：
10.1097/pdm.0b013e31815d0588
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发表时间：
2008-09-01
期刊：
影响因子：
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通讯作者：
Daren, Shi
中科院分区：
文献类型：
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作者：
Baohua, Yu;Xiaoyan, Zhou;Daren, Shi
PI3K/AKT通路可能以尚不清楚的机制参与某些弥漫性大b细胞淋巴瘤（DLBCL）的发展。利用基于聚合酶链反应的序列分析，研究了76例原代人DLBCL、3株DLBCL细胞系（LY1、LY8和LY10）和9个相关样本中PIK3CA外显子9和20的突变，以评估DLBCL中PIK3CA突变与PI3K/AKT通路激活的可能相关性。Western blot和免疫组化检测3株DLBCL细胞株和76例原代DLBCL细胞的AKT磷酸化水平。3种细胞系均显示高水平的pAKT， 72.4%（55/76）的dlbcl表达不同水平的pAKT，表明AKT被激活。然而，在3个细胞系中，PIK3CA的外显子9和20均未发现突变。76例原发性dlbcl中仅有1例（1.32%）存在外显子9突变，未检测到外显子20突变。突变病例包含3个突变点。一个是C . 1634a >C，导致E545A，这是之前报道的热点。另外2个是新的C . 1658g >C和C . 1659delt移码突变。我们得出结论，PI3K/AKT通路在DLBCL中被激活，PIK3CA在DLBCL中很少发生突变，这表明可能存在一些其他的PI3K通路激活机制在DLBCL中起作用。
The PI3K/AKT pathway might be involved in the development of some certain diffuse large B-cell lymphoma (DLBCL) by as-yet unclear mechanisms. PIK3CA mutations in exons 9 and 20 were investigated in 76 primary human DLBCLs, 3 DLBCL cell lines (LY1, LY8, and LY10), and 9 related samples using polymerase chain reaction-based sequence analysis to assess the possible relevance of PIK3CA mutations in DLBCL to the PI3K/AKT pathway activation. AKT phosphorylation (pAKT) of 3 DLBCL cell lines and 76 primary DLBCL samples was also detected by Western blot and immunohistochemistry. All 3 cell lines showed high levels of pAKT, and 72.4% (55/76) of the DLBCLs expressed pAKT at various levels, indicating the activation of AKT. However, no mutation was found in exons 9 or 20 in PIK3CA in any of the 3 cell lines. Only 1 out of 76 primary DLBCLs (1.32%) harbored an exon 9 mutation, and no exon 20 mutation was detected. The case with mutations contained 3 mutation points. One was c.1634A>C resulting in E545A, which was in a previously reported hotspot. The other 2 were novel c.1658G>C and c.1659delT frameshift mutations. We conclude that the PI3K/AKT pathway is activated in DLBCL and that PIK3CA is rarely mutated in DLBCL, indicating there could be some other PI3K-pathway activation mechanisms operative in DLBCL.