Translational Oncology Laboratory, Avera Cancer Institute, Sioux Falls, SD 57105, USA.
Department of Internal Medicine, SSOM, University of South Dakota, Sioux Falls, SD 57105, USA.
Int J Mol Sci. 2019 Nov 15;20(22):5732. doi: 10.3390/ijms20225732.
The chromosome is a functionally dynamic structure. The dynamic nature of chromosome functionally connects it to almost every event within a cell, in health and sickness. Chromatin remodeling system acts in unison with the cell survival pathway in mediating a variety of cellular functions, including mitosis, differentiation, DNA damage repair, and apoptosis. In humans, the 16 SWI/SNF complexes are a class of nucleosome remodelers, and ARID1A, an epigenetic tumor suppressor, is a member of mammalian 17 chromatin remodeling complex, SWI/SNF. Alterations of chromatin remodeling system contribute to tumorigenic events in various cancers, including ovarian cancers. Oncogenic changes of genes of the PI3K pathway are one of the potential genetic determinants of ovarian carcinomas. In this review, we present the data demonstrating the co-occurrence of mutations of ARID1A and the PI3K pathway in our cohort of ovarian cancers from the Avera Cancer Institute (SD, USA). Taking into account data from our cohort and the cBioPortal, we interrogate the opportunity provided by this co-occurrence in the context of mutation-driven signals in the life cycle of a tumor cell and its response to the targeted anti-tumor drugs.
染色体是一种具有功能的动态结构。染色体的动态性质使其与细胞内的几乎每一个事件都有功能上的联系，无论是在健康状态还是疾病状态下。染色质重塑系统与细胞存活途径协同作用，介导多种细胞功能，包括有丝分裂、分化、DNA 损伤修复和细胞凋亡。在人类中，16 个 SWI/SNF 复合物是一类核小体重塑因子，而 ARID1A，一种表观遗传肿瘤抑制因子，是哺乳动物 17 个染色质重塑复合物 SWI/SNF 的成员。染色质重塑系统的改变导致了多种癌症中的肿瘤发生事件，包括卵巢癌。PI3K 通路基因的致癌改变是卵巢癌的潜在遗传决定因素之一。在这篇综述中，我们展示了数据，证明了 ARID1A 和 PI3K 通路的突变在我们来自美国南达科他州 Avera 癌症研究所的卵巢癌队列中同时存在。考虑到我们队列和 cBioPortal 的数据，我们探讨了在肿瘤细胞生命周期中的突变驱动信号及其对靶向抗肿瘤药物的反应背景下，这种同时存在所提供的机会。
