Vanharanta Sakari, Wortham Noel C, Laiho Päivi, Sjöberg Jari, Aittomäki Kristiina, Arola Johanna, Tomlinson Ian P, Karhu Auli, Arango Diego, Aaltonen Lauri A
Department of Medical Genetics, University of Helsinki, PO Box 63 (Haartmaninkatu 8), Biomedicum Helsinki, FIN-00014, Finland.
Oncogene. 2005 Sep 29;24(43):6545-54. doi: 10.1038/sj.onc.1208784.
Uterine fibroids are some of the most common tumours of females, but relatively little is known about their molecular basis. Several studies have suggested that deletions on chromosome 7q could have a role in fibroid formation. We analysed 165 sporadic uterine fibroids to define a small 3.2 megabase (Mb) commonly deleted region on 7q22.3-q31.1, flanked by clones AC005070 and AC007567. We also used oligonucleotide microarrays to compare the expression profiles of 10 samples of normal myometrium and 15 fibroids, nine of which displayed 7q-deletions. Activating transcription factor 3, patched homolog (Drosophila), homeo box A5, death-associated protein kinase 1, and retinoic acid receptor responder 3 were downregulated, and excision repair crosscomplementing 3, transcription factor AP-2 gamma and protein kinase C beta 1 were upregulated in fibroids. New pathways were discovered related to fibroid formation. The presence or absence of 7q-deletions did not dramatically affect the global expression pattern of the tumours; changes, however, were observed in genes related to vesicular transport and nucleic acid binding.
子宫肌瘤是女性最常见的肿瘤之一,但人们对其分子基础了解相对较少。多项研究表明,7号染色体长臂缺失可能在肌瘤形成中起作用。我们分析了165个散发性子宫肌瘤,以确定7q22.3-q31.1上一个3.2兆碱基(Mb)的常见缺失小区域,两侧为克隆AC005070和AC007567。我们还使用寡核苷酸微阵列比较了10个正常子宫肌层样本和15个肌瘤的表达谱,其中9个显示有7号染色体长臂缺失。在肌瘤中,激活转录因子3、果蝇patched同源物、同源盒A5、死亡相关蛋白激酶1和视黄酸受体反应蛋白3下调,而切除修复交叉互补3、转录因子AP-2γ和蛋白激酶Cβ1上调。发现了与肌瘤形成相关的新途径。7号染色体长臂缺失的存在与否并未显著影响肿瘤的整体表达模式;然而,在与囊泡运输和核酸结合相关的基因中观察到了变化。