Differential DNA Methylation in Prostate Tumors from Puerto Rican Men.

Differential DNA Methylation in Prostate Tumors from Puerto Rican Men.
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波多黎各男性前列腺癌的差异DNA甲基化。

DOI:
10.3390/ijms22020733
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发表时间:
2021-01-13
影响因子:
5.6
通讯作者:
Park JY
Park JY
中科院分区:
生物学2区
文献类型:
--
作者:
Ruiz-Deya G;Matta J;Encarnación-Medina J;Ortiz-Sanchéz C;Dutil J;Putney R;Berglund A;Dhillon J;Kim Y;Park JY

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2020年,美国估计约有191,930例新的前列腺癌(PCA)病例。西班牙裔/拉丁裔(H/L)是美国第二大种族/民族群体。这项研究旨在评估攻击性和惰性前列腺癌之间的甲基化模式,包括DNA修复基因以及血统比例。收集根据Gleason评分分为侵袭性(n=11)和惰性(n=13)的前列腺癌。肿瘤和邻近正常组织在H&E(血毒素和曙红)玻片上进行注释,并通过大体解剖提取。使用Illumina 850K DNA甲基化平台评估甲基化模式。使用BioConductor程序包处理原始数据。使用混合体(k=3)估计全球血统比例。包括AOX1在内的108个基因在肿瘤样本中被差异甲基化。在PCa侵袭性方面,共鉴定出6个高甲基化基因(RREB1、FAM71F2、JMJD1C、COL5A3、RAE1和GABRQ)和11个低甲基化基因(COL9A2、FAM179A、SLC17A2、PDE10A、PLEKHS1、TNNI2、OR51A4、RNF169、SPNS2、ADAMTSL5和CYP4F12)。发现了两个显著差异甲基化的DNA修复基因JMJD1C和RNF169。非洲人、欧洲人和土著美国人的血统比例结果分别为24.1%、64.2%和11.7%。确定H/L人群中与前列腺癌相关的DNA甲基化模式,以及与攻击性和DNA修复相关的特定模式,是了解该人群中前列腺癌的关键。
In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.
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