Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.
Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.
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DOI：
10.3390/cancers13071506
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发表时间：
2021-03-25
期刊：
影响因子：
5.2
通讯作者：
Spinella MJ
中科院分区：
文献类型：
--
作者：
Singh R;Fazal Z;Freemantle SJ;Spinella MJ
这篇简短的综述集中在表观遗传学在睾丸癌中的作用。开发了一个工作模型，该模型假设驱动睾丸癌恶性的表观遗传特征也使这些肿瘤能够通过化疗以高速率治愈。化疗耐药性可能通过恶性肿瘤和化疗敏感性的表观遗传解偶联而发生，这种情况可能适用于基于表观遗传的治疗。与许多常见的实体瘤相比，大多数睾丸生殖细胞肿瘤（TGCT）的主要遗传驱动因素尚不清楚。几十年来，人们一直关注TGCT中的基因组改变，包括对染色体12 p拷贝数几乎普遍增加的认识，但未能发现特殊的驱动基因，特别是在可用于治疗的基因中。到目前为止，TGCT患者已经错过了治疗大多数其他恶性肿瘤的靶向治疗的好处。在过去的十年中，人们越来越认识到表观遗传学可能在TGCT的病因、进展和对常规化疗的超敏反应中发挥特别突出的作用。虽然遗传学无疑在TGCT生物学中起着重要作用，但这篇小型综述将重点关注睾丸癌的表观遗传“状态”或特征，重点关注与TGCT易感性，启动，进展和对化疗反应相关的DNA甲基化，组蛋白修饰和miRNA。此外，我们对TGCT的表观遗传学治疗和表观遗传学生物标志物开发的现状进行了评论。最后，我们提出了一个统一的“岩石和一个艰难的地方”或“分化或死亡”模型，其中TGCT的致瘤性和可治愈性都依赖于常见的，但仍然不明确的表观遗传状态。
This minireview focuses on the role of epigenetics in testicular cancer. A working model is developed that postulates that epigenetic features that drive testicular cancer malignancy also enable these tumors to be cured at a high rate with chemotherapy. Chemoresistance may occur by epigenetic uncoupling of malignancy and chemosensitivity, a scenario that may be amenable to epigenetic-based therapies. Compared to many common solid tumors, the main genetic drivers of most testicular germ cell tumors (TGCTs) are unknown. Decades of focus on genomic alterations in TGCTs including awareness of a near universal increase in copies of chromosome 12p have failed to uncover exceptional driver genes, especially in genes that can be targeted therapeutically. Thus far, TGCT patients have missed out on the benefits of targeted therapies available to treat most other malignancies. In the past decade there has been a greater appreciation that epigenetics may play an especially prominent role in TGCT etiology, progression, and hypersensitivity to conventional chemotherapy. While genetics undoubtedly plays a role in TGCT biology, this mini-review will focus on the epigenetic “states” or features of testicular cancer, with an emphasis on DNA methylation, histone modifications, and miRNAs associated with TGCT susceptibility, initiation, progression, and response to chemotherapy. In addition, we comment on the current status of epigenetic-based therapy and epigenetic biomarker development for TGCTs. Finally, we suggest a unifying “rock and a hard place” or “differentiate or die” model where the tumorigenicity and curability of TGCTs are both dependent on common but still ill-defined epigenetic states.
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影响因子：
--
作者：
Albany C;Hever-Jardine MP;von Herrmann KM;Yim CY;Tam J;Warzecha JM;Shin L;Bock SE;Curran BS;Chaudhry AS;Kim F;Sandusky GE;Taverna P;Freemantle SJ;Christensen BC;Einhorn LH;Spinella MJ
通讯作者：
Spinella MJ
影响因子：
30.8
作者：
Chung, Charles C.;Kanetsky, Peter A.;Wang, Zhaoming;Hildebrandt, Michelle A. T.;Koster, Roelof;Skotheim, Rolf I.;Kratz, Christian P.;Turnbull, Clare;Cortessis, Victoria K.;Bakken, Anne C.;Bishop, D. Timothy;Cook, Michael B.;Erickson, R. Loren;Fossa, Sophie D.;Jacobs, Kevin B.;Korde, Larissa A.;Kraggerud, Sigrid M.;Lothe, Ragnhild A.;Loud, Jennifer T.;Rahman, Nazneen;Skinner, Eila C.;Thomas, Duncan C.;Wu, Xifeng;Yeager, Meredith;Schumacher, Fredrick R.;Greene, Mark H.;Schwartz, Stephen M.;McGlynn, Katherine A.;Chanock, Stephen J.;Nathanson, Katherine L.
通讯作者：
Nathanson, Katherine L.
影响因子：
3.9
作者：
Bo, Hao;Cao, Ke;Fan, Liqing
通讯作者：
Fan, Liqing
影响因子：
3.7
作者：
Biswal BK;Beyrouthy MJ;Hever-Jardine MP;Armstrong D;Tomlinson CR;Christensen BC;Marsit CJ;Spinella MJ
通讯作者：
Spinella MJ
影响因子：
3.8
作者：
Cierna, Zuzana;Miskovska, Vera;Chovanec, Miroslav
通讯作者：
Chovanec, Miroslav