Emergence of the Noncoding Cancer Genome: A Target of Genetic and Epigenetic Alterations

Zhou, Stanley; Treloar, Aislinn E.; Lupien, Mathieu

doi:10.1158/2159-8290.cd-16-0745

Cited by 82 publications

(62 citation statements)

References 200 publications

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“…Previous studies have shown that tumors exhibit both genetic and epigenetic heterogeneity within cell populations, and that epigenetic changes, such as DNA methylation and/or histone modifications, accumulate in the genome throughout oncogenesis (12)(13)(14)(15). This dynamic landscape may permit the introduction of adaptive ALK-independent mechanisms of drug resistance within targeted cells.…”

Section: Introductionmentioning

confidence: 99%

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

et al. 2018

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“…Of these, mutations occurring in cis‐regulatory elements (i.e., enhancers and promoters) are of particular interest, as they can directly alter expression of associated gene products, by directly or indirectly altering DNA binding of TFs (Deplancke et al, ; Shi et al, ). Such mutations are frequent in breast cancer (Bailey et al, ; Zhou et al, ; Rheinbay et al, ; Gyorffy et al, ), but their significance is generally unclear (Nik‐Zainal et al, ). However, mutations in ESR1 enhancer sequences found in ~ 7% of breast cancers have now been shown to be responsible for altering ESR1 expression by modulating TF binding activity (Bailey et al, ).…”

Section: Altered Transcriptional Regulation In Human Breast Cancersmentioning

confidence: 99%

“…Data are drawn from the 993 breast cancer cases in the TCGA PanCancer Atlas study analyzed and plotted via cBioportal (http://www.cbioportal.org). (Bailey et al, 2016;Zhou et al, 2016;Rheinbay et al, 2017;Gyorffy et al, 2018), but their significance is generally unclear (Nik-Zainal et al, 2016). However, mutations in ESR1 enhancer sequences found in~7% of breast cancers have now been shown to be responsible for altering ESR1 expression by modulating TF binding activity (Bailey et al, 2016).…”

Section: Ube2tmentioning

confidence: 99%

Transcriptional regulation of normal human mammary cell heterogeneity and its perturbation in breast cancer

et al. 2019

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The mammary gland in adult women consists of biologically distinct cell types that differ in their surface phenotypes. Isolation and molecular characterization of these subpopulations of mammary cells have provided extensive insights into their different transcriptional programs and regulation. This information is now serving as a baseline for interpreting the heterogeneous features of human breast cancers. Examination of breast cancer mutational profiles further indicates that most have undergone a complex evolutionary process even before being detected. The consequent intra‐tumoral as well as inter‐tumoral heterogeneity of these cancers thus poses major challenges to deriving information from early and hence likely pervasive changes in potential therapeutic interest. Recently described reproducible and efficient methods for generating human breast cancers de novo in immunodeficient mice transplanted with genetically altered primary cells now offer a promising alternative to investigate initial stages of human breast cancer development. In this review, we summarize current knowledge about key transcriptional regulatory processes operative in these partially characterized subpopulations of normal human mammary cells and effects of disrupting these processes in experimentally produced human breast cancers.

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“…In the past decades, lots of ncRNAs have been found, such as ribosomal RNA (rRNA), transfer RNA (tRNA), small nuclear RNA (snRNA) and microRNA (miRNA) as well as long non‐coding RNA (lncRNA). Aberrations within the non‐coding genome are major decisive factors contributed to human diseases . Among these non‐protein‐coding transcripts, lncRNAs, defined as longer than 200 nucleotides with little or no protein‐coding ability, have emerged as essential regulators in diverse biological processes .…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between long non‐coding RNAs and Wnt/β‐catenin signalling in cancer

Yang

Shen

et al. 2018

J Cellular Molecular Medi

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Long non‐coding RNAs (lncRNAs) are non‐protein‐coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/β‐catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/β‐catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/β‐catenin signalling pathway‐related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/β‐catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/β‐catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/β‐catenin signalling pathway may be a feasible therapeutic method in the future.

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Emergence of the Noncoding Cancer Genome: A Target of Genetic and Epigenetic Alterations

Cited by 82 publications

References 200 publications

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

Transcriptional regulation of normal human mammary cell heterogeneity and its perturbation in breast cancer

Crosstalk between long non‐coding RNAs and Wnt/β‐catenin signalling in cancer

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