Genomic Signatures in HPV-Associated Tumors.
Genomic Signatures in HPV-Associated Tumors.
复制标题
DOI：
10.3390/v13101998
复制
发表时间：
2021-10-05
期刊：
影响因子：
--
通讯作者：
Higginson DS
中科院分区：
文献类型：
--
作者：
Hussain SS;Lundine D;Leeman JE;Higginson DS
乳头瘤病毒通过调节G1/S期细胞周期转换来促进S期DNA合成，这是病毒复制的必要条件。人乳头瘤病毒（HPV）E6和E7癌蛋白介导细胞周期调节因子p53和Rb的降解，这两种基因是所有癌症中最普遍破坏的肿瘤抑制基因。G1/S检查点在正常细胞中被激活，以便在继续复制DNA并冒传播未修复错误的风险之前有足够的时间在G1中进行DNA修复。TP 53通路抑制多种此类错误，包括易位、拷贝数改变和非整倍性，因此在HPV相关肿瘤中发现这些错误，类似于具有TP 53破坏的其他机制的HPV阴性肿瘤。然而，E6和E7维持了多种其他病毒-宿主相互作用，这些相互作用直接破坏了越来越多的其他DNA修复和染色质重塑因子，这意味着HPV特异性修复缺陷。此外，HPV相关鳞状细胞癌肿瘤与HPV阴性肿瘤相比，对DNA损伤剂的临床反应不同。本综述的重点是整合三类观察：（1）临床前了解HPV对DNA修复的影响，（2）HPV相关肿瘤基因组中DNA修复的基因组特征，（3）HPV相关肿瘤对DNA损伤剂的临床反应。目的是试图解释为什么HPV相关肿瘤对DNA损伤剂反应如此之好，识别缺失的片段，并建议临床策略可用于进一步改善这些癌症的治疗。
Papillomaviruses dysregulate the G1/S cell cycle transition in order to promote DNA synthesis in S phase, which is a requirement for viral replication. The human papillomaviruses (HPV) E6 and E7 oncoproteins mediate degradation of the cell cycle regulators p53 and Rb, which are two of the most universally disrupted tumor-suppressor genes in all of cancer. The G1/S checkpoint is activated in normal cells to allow sufficient time for DNA repair in G1 before proceeding to replicate DNA and risk propagating unrepaired errors. The TP53 pathway suppresses a variety of such errors, including translocation, copy number alterations, and aneuploidy, which are thus found in HPV-associated tumors similarly to HPV-negative tumors with other mechanisms of TP53 disruption. However, E6 and E7 maintain a variety of other virus–host interactions that directly disrupt a growing list of other DNA repair and chromatin remodeling factors, implying HPV-specific repair deficiencies. In addition, HPV-associated squamous cell carcinomas tumors clinically respond differently to DNA damaging agents compared to their HPV negative counterparts. The focus of this review is to integrate three categories of observations: (1) pre-clinical understanding as to the effect of HPV on DNA repair, (2) genomic signatures of DNA repair in HPV-associated tumor genomes, and (3) clinical responses of HPV-associated tumors to DNA damaging agents. The goals are to try to explain why HPV-associated tumors respond so well to DNA damaging agents, identify missing pieces, and suggest clinical strategies could be used to further improve treatment of these cancers.
登录
查看更多内容
影响因子：
16
作者：
Deriano, Ludovic;Stracker, Travis H.;Baker, Annalee;Petrini, John H. J.;Roth, David B.
通讯作者：
Roth, David B.
影响因子：
6.4
作者：
Das, Dipon;Bristol, Molly L.;Morgan, Iain M.
通讯作者：
Morgan, Iain M.
影响因子：
5.4
作者：
Fradet-Turcotte, Amelie;Bergeron-Labrecque, Fanny;Archambault, Jacques
通讯作者：
Archambault, Jacques
影响因子：
7
作者：
Gillison, Maura L.;Akagi, Keiko;Symer, David E.
通讯作者：
Symer, David E.
影响因子：
21.3
作者：
Dev H;Chiang TW;Lescale C;de Krijger I;Martin AG;Pilger D;Coates J;Sczaniecka-Clift M;Wei W;Ostermaier M;Herzog M;Lam J;Shea A;Demir M;Wu Q;Yang F;Fu B;Lai Z;Balmus G;Belotserkovskaya R;Serra V;O'Connor MJ;Bruna A;Beli P;Pellegrini L;Caldas C;Deriano L;Jacobs JJL;Galanty Y;Jackson SP
通讯作者：
Jackson SP