Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.
Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.
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DOI：
10.1186/bcr3612
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发表时间：
2014-02-03
期刊：
影响因子：
--
通讯作者：
Hansen L
中科院分区：
文献类型：
--
作者：
Wojdacz TK;Windeløv JA;Thestrup BB;Damsgaard TE;Overgaard J;Hansen L
尽管有相似的临床和病理特征，但大量乳腺癌患者经历了不同的疾病结局。这一点，加上乳腺癌的发病率在世界范围内不断增长的事实，强调了迫切需要鉴定新的生物标志物，用于早期癌症检测和患者分层。我们使用超高分辨率微阵列比较乳腺癌（n = 20）和非恶性乳腺组织（n = 5）的全基因组甲基化模式。在一组乳腺癌（n = 275）和非恶性对照（n = 74）的病例对照研究中，使用甲基化敏感性高分辨率熔解（MS-HRM）验证了发现的差异甲基化区域（DMR）子集的生物标志物特性。根据芯片结果，我们选择了19个DMR进行大规模病例和对照筛查。筛选结果的分析显示，与对照组织中的水平相比，所有测试的DMR在癌组织中显示出甲基化的显著增加。有趣的是，我们观察到两种类型的基因座特异性甲基化，基因座在癌变过程中主要经历完全甲基化或异质甲基化。几乎所有检测的DMR（19例中的17例）在非恶性乳腺组织中均显示低水平甲基化，与病例中的基因座特异性甲基化模式无关。特定的基因座在癌变过程中可以发生异质性或完全甲基化，而在癌症中高甲基化的基因座在非恶性组织中经常显示低水平的甲基化。
Despite similar clinical and pathological features, large numbers of breast cancer patients experience different outcomes of the disease. This, together with the fact that the incidence of breast cancer is growing worldwide, emphasizes an urgent need for identification of new biomarkers for early cancer detection and stratification of patients. We used ultrahigh-resolution microarrays to compare genomewide methylation patterns of breast carcinomas (n = 20) and nonmalignant breast tissue (n = 5). Biomarker properties of a subset of discovered differentially methylated regions (DMRs) were validated using methylation-sensitive high-resolution melting (MS-HRM) in a case–control study on a panel of breast carcinomas (n = 275) and non-malignant controls (n = 74). On the basis of microarray results, we selected 19 DMRs for large-scale screening of cases and controls. Analysis of the screening results showed that all DMRs tested displayed significant gains of methylation in the cancer tissue compared to the levels in control tissue. Interestingly, we observed two types of locus-specific methylation, with loci undergoing either predominantly full or heterogeneous methylation during carcinogenesis. Almost all tested DMRs (17 of 19) displayed low-level methylation in nonmalignant breast tissue, independently of locus-specific methylation patterns in cases. Specific loci can undergo either heterogeneous or full methylation during carcinogenesis, and loci hypermethylated in cancer frequently show low-level methylation in nonmalignant tissue.
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DOI：
10.1056/nejmoa1110000
发表时间：
2012-01-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ewing CM;Ray AM;Lange EM;Zuhlke KA;Robbins CM;Tembe WD;Wiley KE;Isaacs SD;Johng D;Wang Y;Bizon C;Yan G;Gielzak M;Partin AW;Shanmugam V;Izatt T;Sinari S;Craig DW;Zheng SL;Walsh PC;Montie JE;Xu J;Carpten JD;Isaacs WB;Cooney KA
通讯作者：
Cooney KA
影响因子：
14.8
作者：
Wojdacz, Tomasz K.;Dobrovic, Alexander;Hansen, Lise Lotte
通讯作者：
Hansen, Lise Lotte
影响因子：
3.7
作者：
Migheli F;Stoccoro A;Coppedè F;Wan Omar WA;Failli A;Consolini R;Seccia M;Spisni R;Miccoli P;Mathers JC;Migliore L
通讯作者：
Migliore L
影响因子：
2.8
作者：
Hansen, LL;Andersen, J;Kruse, TA
通讯作者：
Kruse, TA
影响因子：
11.2
作者：
Stefanska, Barbara;Huang, Jian;Szyf, Moshe
通讯作者：
Szyf, Moshe