Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations.
Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations.
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DOI：
10.1158/1940-6207.capr-09-0078
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Knudson AG
中科院分区：
文献类型：
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作者：
Bellacosa A;Godwin AK;Peri S;Devarajan K;Caretti E;Vanderveer L;Bove B;Slater C;Zhou Y;Daly M;Howard S;Campbell KS;Nicolas E;Yeung AT;Clapper ML;Crowell JA;Lynch HT;Ross E;Kopelovich L;Knudson AG
我们假设在肿瘤抑制基因中携带单一遗传"命中"的细胞表达改变的mRNA库，其可以识别可以延迟甚至防止进展为癌的措施的靶点。我们在这里报告的原代乳腺和卵巢上皮细胞培养BRCA1和BRCA2突变载体和控制的转录组。我们的比较分析确定了两种组织中两种突变的基因表达的多种变化，这些变化通过实时RT-PCR分析进行了独立验证。一些差异表达的基因以前曾被提出作为癌症标志物，包括乳腺癌中的乳房珠蛋白和卵巢癌中的血清淀粉样蛋白。这些研究结果表明，杂合性突变的肿瘤抑制基因可以改变表型正常的上皮细胞的表达谱在基因特异性的方式，这些可检测的影响“一击”代表肿瘤发生的早期分子变化，可能作为新的生物标志物的癌症风险和化学预防的目标。
We hypothesized that cells bearing a single inherited “hit” in a tumor suppressor gene express an altered mRNA repertoire that may identify targets for measures that could delay or even prevent progression to carcinoma. We report here on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation-carriers and controls. Our comparison analyses identified multiple changes in gene expression, in both tissues for both mutations, that were validated independently validated by real-time RT-PCR analysis. Several of the differentially expressed genes had been previously proposed as cancer markers, including mammaglobin in breast cancer and serum amyloid in ovarian cancer. These findings demonstrate that heterozygosity for a mutant tumor suppressor gene can alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner; these detectable effects of “one-hit” represent early molecular changes in tumorigenesis that may serve as novel biomarkers of cancer risk and as targets for chemoprevention.