Analysis of the mitogen-activated protein kinase kinase 4 (MAP2K4) tumor suppressor gene in ovarian cancer.
Analysis of the mitogen-activated protein kinase kinase 4 (MAP2K4) tumor suppressor gene in ovarian cancer.
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DOI：
10.1186/1471-2407-11-173
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发表时间：
2011-05-17
期刊：
影响因子：
3.8
通讯作者：
Gorringe KL
中科院分区：
文献类型：
--
作者：
Davis SJ;Choong DY;Ramakrishna M;Ryland GL;Campbell IG;Gorringe KL
MAP2K4是一种推定的肿瘤和转移抑制基因，在各种癌症类型中经常被发现缺失。我们的目的是对该基因进行全面分析，以评估其与卵巢癌的关系。我们使用高分辨率熔体分析筛选了149例原发性卵巢肿瘤的MAP2K4突变，并使用甲基化特异性单链构象多态性分析筛选了39例肿瘤的启动子甲基化。我们还使用公开可用的表达和拷贝数数组数据考虑了MAP2K4变化的临床影响。最后，我们使用siRNA来测量降低细胞系中MAP2K4表达的效果。除了先前检测到的4个纯合缺失外，我们还在一个卵巢肿瘤中发现了一个纯合的16 bp截断缺失和一个杂合的4 bp缺失。未检测到启动子甲基化。MAP2K4纯合子失活的频率为5.6%，在高级别浆液病例中为9.8%。在38%的样本中观察到MAP2K4的半合子缺失。在三个微阵列数据集中，拷贝数和表达有显著的相关性。在一个表达阵列数据集中，MAP2K4表达与总生存率之间存在显著相关性，但在独立数据集中未得到证实。MAP2K4 siRNA处理JAM和HOSE6.3细胞系后，细胞增殖有所减少。在我们的队列中，MAP2K4是卵巢癌基因失活的靶点，仅限于高级别浆液性癌和子宫内膜样癌。
MAP2K4 is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer. We screened for mutations in MAP2K4 using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in MAP2K4 using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing MAP2K4 expression in cell lines. In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of MAP2K4 homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of MAP2K4 was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between MAP2K4 expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with MAP2K4 siRNA showed some reduction in proliferation. MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.7
作者：
Ramakrishna M;Williams LH;Boyle SE;Bearfoot JL;Sridhar A;Speed TP;Gorringe KL;Campbell IG
通讯作者：
Campbell IG
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56.9
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通讯作者：
Lapadat, R
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Tsao, SW;Wong, N;Wong, YC
通讯作者：
Wong, YC
影响因子：
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作者：
XIA, ZG;DICKENS, M;GREENBERG, ME
通讯作者：
GREENBERG, ME