DNA hypermethylation of the ZNF132 gene participates in the clinicopathological aggressiveness of 'pan-negative'-type lung adenocarcinomas.
DNA hypermethylation of the ZNF132 gene participates in the clinicopathological aggressiveness of 'pan-negative'-type lung adenocarcinomas.
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DOI：
10.1093/carcin/bgaa115
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发表时间：
2021-02-25
期刊：
影响因子：
4.7
通讯作者：
Arai E
中科院分区：
文献类型：
--
作者：
Hamada K;Tian Y;Fujimoto M;Takahashi Y;Kohno T;Tsuta K;Watanabe SI;Yoshida T;Asamura H;Kanai Y;Arai E
虽然以前的一些研究已经检查了肺腺癌的表观基因组改变，但表观基因组事件与基因组驱动突变之间的相关性尚未完全阐明。使用Infinium HumanMethylation27 BeadChip进行单cpg分辨率全基因组DNA甲基化分析，使用来自肺腺癌患者的相邻正常肺组织(N)和相应的肿瘤组织(T)的162对配对样本。研究了DNA甲基化数据与临床病理参数和基因组驱动突变（即EGFR、KRAS、BRAF和HER2突变以及涉及ALK、RET和ROS1的融合）之间的相关性。来自N个样本的12629个探针的DNA甲基化水平与无复发生存率显著相关。主成分分析显示，癌前N期不同的DNA甲基化谱倾向于不诱导特定的基因组驱动畸变。在从N到T的转变过程中，大多数显示出显著DNA甲基化改变的基因是由两个或多个驱动畸变组共享的。ZNF132仅在泛阴性组出现DNA超甲基化，且与血管侵袭相关，经小干扰RNA敲除后，检测癌细胞的增殖、凋亡和迁移。ZNF132敲低导致细胞迁移能力增强，而不是增加细胞生长或减少细胞凋亡。我们得出结论，ZNF132基因的DNA高甲基化参与了“泛阴性”肺腺癌的临床病理侵袭性。此外，癌前阶段的DNA甲基化改变可能决定肿瘤的侵袭性，驱动突变后积累的这种改变可能通过改变基因表达来改变临床病理特征。甲基组分析表明，癌前阶段的DNA甲基化改变可能决定了肺腺癌的侵袭性，这种改变在驱动突变（如ZNF132的表观遗传沉默）后积累，另外还改变了临床病理特征。
Although some previous studies have examined epigenomic alterations in lung adenocarcinomas, correlations between epigenomic events and genomic driver mutations have not been fully elucidated. Single-CpG resolution genome-wide DNA methylation analysis with the Infinium HumanMethylation27 BeadChip was performed using 162 paired samples of adjacent normal lung tissue (N) and the corresponding tumorous tissue (T) from patients with lung adenocarcinomas. Correlations between DNA methylation data on the one hand and clinicopathological parameters and genomic driver mutations, i.e. mutations of EGFR, KRAS, BRAF and HER2 and fusions involving ALK, RET and ROS1, were examined. DNA methylation levels in 12 629 probes from N samples were significantly correlated with recurrence-free survival. Principal component analysis revealed that distinct DNA methylation profiles at the precancerous N stage tended not to induce specific genomic driver aberrations. Most of the genes showing significant DNA methylation alterations during transition from N to T were shared by two or more driver aberration groups. After small interfering RNA knockdown of ZNF132, which showed DNA hypermethylation only in the pan-negative group and was correlated with vascular invasion, the proliferation, apoptosis and migration of cancer cell lines were examined. ZNF132 knockdown led to increased cell migration ability, rather than increased cell growth or reduced apoptosis. We concluded that DNA hypermethylation of the ZNF132 gene participates in the clinicopathological aggressiveness of ‘pan-negative’ lung adenocarcinomas. In addition, DNA methylation alterations at the precancerous stage may determine tumor aggressiveness, and such alterations that accumulate after driver mutation may additionally modify clinicopathological features through alterations of gene expression. Methylome analysis has revealed that DNA methylation alterations at the precancerous stage may determine the aggressiveness of lung adenocarcinomas and that such alterations accumulating after driver mutation, e.g. epigenetic silencing of ZNF132, additionally modify the clinicopathological features.
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影响因子：
--
作者：
Quek K;Li J;Estecio M;Zhang J;Fujimoto J;Roarty E;Little L;Chow CW;Song X;Behrens C;Chen T;William WN;Swisher S;Heymach J;Wistuba I;Zhang J;Futreal A;Zhang J
通讯作者：
Zhang J
影响因子：
6.6
作者：
Bjaanæs MM;Fleischer T;Halvorsen AR;Daunay A;Busato F;Solberg S;Jørgensen L;Kure E;Edvardsen H;Børresen-Dale AL;Brustugun OT;Tost J;Kristensen V;Helland Å
通讯作者：
Helland Å
影响因子：
3.7
作者：
Kanai Y;Arai E
通讯作者：
Arai E
影响因子：
--
作者：
Husni, Ryan Edbert;Shiba-Ishii, Aya;Noguchi, Masayuki
通讯作者：
Noguchi, Masayuki
DOI：
10.1097/jto.0000000000000560
发表时间：
2015-07
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Robles AI;Arai E;Mathé EA;Okayama H;Schetter AJ;Brown D;Petersen D;Bowman ED;Noro R;Welsh JA;Edelman DC;Stevenson HS;Wang Y;Tsuchiya N;Kohno T;Skaug V;Mollerup S;Haugen A;Meltzer PS;Yokota J;Kanai Y;Harris CC
通讯作者：
Harris CC