Epigenome-wide association study in hepatocellular carcinoma: Identification of stochastic epigenetic mutations through an innovative statistical approach.
Epigenome-wide association study in hepatocellular carcinoma: Identification of stochastic epigenetic mutations through an innovative statistical approach.
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DOI：
10.18632/oncotarget.17462
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发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Vitale G
中科院分区：
文献类型：
--
作者：
Gentilini D;Scala S;Gaudenzi G;Garagnani P;Capri M;Cescon M;Grazi GL;Bacalini MG;Pisoni S;Dicitore A;Circelli L;Santagata S;Izzo F;Di Blasio AM;Persani L;Franceschi C;Vitale G
肝细胞癌（HCC）是由遗传和表观遗传改变的积累引起的。我们使用Infinium HumanMethylation 450K BeadChip阵列研究了69对HCC和邻近非癌性肝组织的全基因组DNA甲基化谱。采用一种创新的分析方法来识别HCC中的随机表观遗传突变（SEMs）。HCC和肿瘤周围组织表现出不同的表观遗传谱，主要特征是HCC中DNA甲基化的缺失。SEMs的总数在HCC肿瘤中（中位数：77,370）明显高于瘤周组织（中位数：5,656），且与肿瘤分级相关。在肿瘤周围组织中测量的SEMs与乙型和/或丙型肝炎病毒感染状态之间存在显著的正相关。超过90%的HCC肿瘤样本共享有限数量的sem，并且从未出现在瘤周组织中。该分析鉴定出4个表观遗传调控的候选基因（AJAP1, ADARB2, PTPRN2, SDK1），它们可能参与HCC的发病机制。总之，HCC显示甲基化谱完全不受调节，与邻近的非癌性肝组织非常遥远。扫描电镜分析为进一步了解HCC的肿瘤发生过程提供了有价值的线索。
Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC. HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade. A significant positive association emerged between SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection status. A restricted number of SEMs resulted to be shared by more than 90% of HCC tumor samples and never present in peritumoral tissue. This analysis allowed the identification of four epigenetically regulated candidate genes (AJAP1, ADARB2, PTPRN2, SDK1), potentially involved in the pathogenesis of HCC. In conclusion, HCC showed a methylation profile completely deregulated and very far from adjacent non-cancerous liver tissues. The SEM analysis provided valuable clues for further investigations in understanding the process of tumorigenesis in HCC.
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RNA-Seq 分析生成全面的转录组景观并揭示肝细胞癌中复杂的转录模式。
影响因子：
3.7
作者：
Huang Q;Lin B;Liu H;Ma X;Mo F;Yu W;Li L;Li H;Tian T;Wu D;Shen F;Xing J;Chen ZN
通讯作者：
Chen ZN
影响因子：
7.8
作者：
Capri M;Olivieri F;Lanzarini C;Remondini D;Borelli V;Lazzarini R;Graciotti L;Albertini MC;Bellavista E;Santoro A;Biondi F;Tagliafico E;Tenedini E;Morsiani C;Pizza G;Vasuri F;D'Errico A;Dazzi A;Pellegrini S;Magenta A;D'Agostino M;Capogrossi MC;Cescon M;Rippo MR;Procopio AD;Franceschi C;Grazi GL
通讯作者：
Grazi GL
影响因子：
7.4
作者：
Marra M;Sordelli IM;Lombardi A;Lamberti M;Tarantino L;Giudice A;Stiuso P;Abbruzzese A;Sperlongano R;Accardo M;Agresti M;Caraglia M;Sperlongano P
通讯作者：
Sperlongano P
影响因子：
8.8
作者：
Stiuso, Paola;Potenza, Nicoletta;Caraglia, Michele
通讯作者：
Caraglia, Michele
影响因子：
--
作者：
Dhanasekaran, Renumathy;Bandoh, Salome;Roberts, Lewis R
通讯作者：
Roberts, Lewis R