Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.
Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.
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DOI：
10.1002/gcc.20692
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发表时间：
2009-10
影响因子：
3.7
通讯作者：
Morton, Cynthia C.
中科院分区：
文献类型：
--
作者：
Hodge, Jennelle C.;Park, Peter J.;Dreyfuss, Jonathan M.;Assil-Kishawi, Iman;Somasundaram, Priya;Semere, Luwam G.;Quade, Bradley J.;Lynch, Allison M.;Stewart, Elizabeth A.;Morton, Cynthia C.
子宫平滑肌瘤（UL）是育龄妇女中最常见的肿瘤，可复发性细胞遗传学异常，包括del(7)（q22q32）。为了建立分子特征，用表达阵列对11名女性的del（7q）和非del（7q）肿瘤进行了FISH或核型分析。我们使用配对t检验的分析表明，这种匹配设计对于消除导致患者变异的基因型和环境的混杂效应至关重要。按全基因组显著性排序的基因列表显示7q22靶区富集。通过对每个样本的del（7q）细胞的百分比进行加权来修改基因列表，以解释这些肿瘤的镶嵌性质，进一步提高了7q22基因的频率。通路分析显示，19个重要的功能网络中有两个与肿瘤的发展有关，最具代表性的途径是蛋白质泛素化，它可以通过稳定癌蛋白和破坏肿瘤抑制蛋白来影响肿瘤的发展。阵列CGH （aCGH）研究确定，唯一一致的基因组失衡是7q22-7q31.1缺失9.5兆碱基。将aCGH数据与del(7q) UL mosacism-weighted表达分析相结合，得出了一个基因列表，这些基因通常被删除，其拷贝数与表达显著降低相关。这些基因包括增殖抑制剂HPB1，其表达缺失与浸润性乳腺癌有关，以及维持有丝分裂完整性的肿瘤抑制因子RINT1。该研究提供了del(7q) UL亚群的分子特征，将为未来肿瘤发病机制的研究提供平台。
Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including del(7)(q22q32). To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t-tests demonstrates this matched design is critical to eliminate confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosacism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis.
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影响因子：
5.3
作者：
Lin, Xiaoqin;Liu, Chang-Ching;Lee, Wen-Hwa
通讯作者：
Lee, Wen-Hwa
影响因子：
3.7
作者：
NILBERT, M;HEIM, S
通讯作者：
HEIM, S
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1016/j.biocel.2008.04.012
发表时间：
2008-01-01
影响因子：
4
作者：
Chang, Fei;Liu, Jie;Deng, Lih-Wen
通讯作者：
Deng, Lih-Wen
影响因子：
3.7
作者：
MASHAL, RD;FEJZO, MLS;SKLAR, J
通讯作者：
SKLAR, J