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Pan-cancer analyses reveal regulation and clinical outcome association of the shelterin complex in cancer

Zhenhua Luo, Weijin Liu, Panpan Sun, Feng Wang, Xuyang Feng
2021 Briefings in Bioinformatics  
However, the detailed mechanisms of shelterin regulation in cancer remain elusive.  ...  In summary, this study provides broad molecular signatures for further functional and therapeutic studies of shelterin, and also represents a systemic approach to characterize key protein complex in cancer  ...  Acknowledgements We would like to thank other members in the lab for discussion and suggestions.  ... 
doi:10.1093/bib/bbaa441 pmid:33497432 fatcat:wrikysq4zbgidmvziucbmzcwwi

Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential

Stina George Fernandes, Rebecca Dsouza, Gouri Pandya, Anuradha Kirtonia, Vinay Tergaonkar, Sook Y. Lee, Manoj Garg, Ekta Khattar
2020 Cancers  
Thus, understanding the role of telomeres and their associated proteins in cancer initiation, progression and treatment is very important.  ...  Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects them from being identified as DNA damage sites.  ...  The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.  ... 
doi:10.3390/cancers12071901 pmid:32674474 pmcid:PMC7409176 fatcat:tcdcyrsiebfetdlibrfznq2xea

Telomere Dysfunction in Chronic Lymphocytic Leukemia

Billy Michael Chelliah Jebaraj, Stephan Stilgenbauer
2021 Frontiers in Oncology  
Different members of the shelterin complex, which form the telomere structure have deregulated expression and POT1 is recurrently mutated in about 3.5% of CLL.  ...  In chronic lymphocytic leukemia (CLL), telomere length is an independent prognostic factor and short telomeres are associated with adverse outcome.  ...  The telomeric repeats are associated with a sixsubunit protein complex called shelterin consisting of TRF1, TRF2, TIN2, TPP1, POT1, and RAP1.  ... 
doi:10.3389/fonc.2020.612665 pmid:33520723 pmcid:PMC7844343 fatcat:argdlg34kbb35fdjzlr733b5ku

Epigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in Gliomas

2017 Genes  
Here, we summarize the genetic background of TMMs in non-malignant cells and in cancer, in addition to clinical and pathological features of gliomas.  ...  ALT is associated with lower tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors by direct mutation and epigenetic activation of the hTERT promoter is well established.  ...  Conflicts of Interest: The authors declare no conflict of interest. The founding sponsors had no role in the writing of the manuscript, and in the decision to publish the manuscript.  ... 
doi:10.3390/genes8050145 pmid:28513547 pmcid:PMC5448019 fatcat:stbp5f2dobhoddz2ruwim3qtee

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Siyuan Zheng, Andrew D. Cherniack, Ninad Dewal, Richard A. Moffitt, Ludmila Danilova, Bradley A. Murray, Antonio M. Lerario, Tobias Else, Theo A. Knijnenburg, Giovanni Ciriello, Seungchan Kim, Guillaume Assie (+257 others)
2016 Cancer Cell  
Genome wide DNA copy number analysis revealed frequent occurrence of massive DNA loss followed by whole genome doubling (WGD) which was associated with aggressive clinical course, suggesting WGD is a hallmark  ...  Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1.  ...  Acknowledgments We are grateful to all the patients and families who contributed to this study, to Ina Felau, Margi Sheth and Jiashan (Julia) Zhang for project management.  ... 
doi:10.1016/j.ccell.2016.04.002 pmid:27165744 pmcid:PMC4864952 fatcat:xj2ms2jchran5aselyejjdvsae

Association between functional TERT promoter polymorphism rs2853669 and cervical cancer risk in South Indian women

Vilvanathan Vinothkumar, Kanagaraj Arun, Ganesan Arunkumar, Sundaramoorthy Revathidevi, Rajendren Ramani, Lakkakula Bhaskar, Avaniyapuram Murugan, Arasambattu Munirajan
2020 Molecular and clinical oncology  
To understand and compare the frequency of the variant allele and its risk association in different cancer types of various populations, the SNP was genotyped in 257 cervical cancer samples and 295 controls  ...  In addition, the overall meta-analysis revealed a significant association of the SNP rs2853669 with other cancer types in different ethnic populations (OR=1.09; 95% CI=1.03-1.16; P=0.004).  ...  Introduction Telomeres are special structures at the ends of the chromosomes consisting of 'TTAGGG' tandem repeat sequences along with its associated protein complex called 'shelterin' (1) .  ... 
doi:10.3892/mco.2020.2003 pmid:32257207 pmcid:PMC7087481 fatcat:5fjmdcvj3je3lahytgekntk4qm

Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases

JinWoo Hong, Chae-Ok Yun
2019 Cells  
Thus, telomere-associated genes in the scope of cancer gene therapy must be inactivated or inhibited to induce anticancer effects.  ...  However, reactivation and overexpression of telomerase are observed in 85% of cancer patients; this process is integral to cancer immortality.  ...  Similar improvements in the longevity of aging mice were achieved by transfer of the TRF1 gene, which is an essential part of the shelterin complex for telomere replication and protection, using AAV9  ... 
doi:10.3390/cells8050392 pmid:31035374 pmcid:PMC6563133 fatcat:w2k3z4pcvrfl7k3s32jn2fb3dq

Role of the Circadian Clock "Death-Loop" in the DNA Damage Response Underpinning Cancer Treatment Resistance

Ninel Miriam Vainshelbaum, Kristine Salmina, Bogdan I. Gerashchenko, Marija Lazovska, Pawel Zayakin, Mark Steven Cragg, Dace Pjanova, Jekaterina Erenpreisa
2022 Cells  
Here, we review the role of the circadian clock (CC) in the resistance of cancer cells to genotoxic treatments in relation to whole-genome duplication (WGD) and telomere-length regulation.  ...  The CC drives the normal cell cycle, tissue differentiation, and reciprocally regulates telomere elongation. However, it is deregulated in embryonic stem cells (ESCs), the early embryo, and cancer.  ...  Acknowledgments: Jekabs Krigerts is acknowledged for the cytometry of WB344 cells. Conflicts of Interest: The authors declare no conflict of interest. Cells 2022, 11, 880  ... 
doi:10.3390/cells11050880 pmid:35269502 pmcid:PMC8909334 fatcat:ddpqavvq5nfk3lbrc2luhmgcdq

Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

Caroline Molinaro, Alain Martoriati, Katia Cailliau
2021 Cancers  
In recent years, technological advances have made it possible to benefit from the principles and mechanisms of DDR to target and eliminate cancer cells.  ...  These monitoring mechanisms ensure the maintenance and the transfer of a correct genome to daughter cells through a selection of DNA repair, cell cycle regulation, and programmed cell death processes.  ...  The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.  ... 
doi:10.3390/cancers13153819 pmid:34359720 pmcid:PMC8345162 fatcat:7e62fiioxjb6jka265tpddum7q

The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia

S N Malek
2012 Oncogene  
Finally, gaps in knowledge regarding the biological and clinical effects of recurrent genomic aberrations or gene mutations on CLL are outlined to provide critical stimuli for future research.  ...  Of the enduring fundamental biological processes that affect the biology and clinical behavior of CLL, few are as central to the pathogenesis of CLL as recurrent acquired genomic copy number aberrations  ...  The analysis of clonal evolution in CLL and effects on clinical outcome are a research opportunity in CLL. 1, [63] [64] [65] Given the anatomic size of 17p deletions in CLL, it is likely that the full  ... 
doi:10.1038/onc.2012.411 pmid:23001040 pmcid:PMC3676480 fatcat:ahv7mvqi7nhsditrkukrcgiuwe

USP7 Is a Master Regulator of Genome Stability

Gabrielle J. Valles, Irina Bezsonova, Roger Woodgate, Nicholas W. Ashton
2020 Frontiers in Cell and Developmental Biology  
In this work, we review the increasingly evident role of USP7 in maintaining genome stability, the links between USP7 deregulation and cancer progression, as well as the rationale of targeting USP7 in  ...  The deubiquitinating enzyme ubiquitin specific protease 7 (USP7) has recently emerged as a key regulator of ubiquitination in the genome stability pathways.  ...  In germ cells and the vast majority of cancer cells, the shelterin complex also contributes to regulating telomere lengthening, either via telomerase-mediated DNA synthesis (active in 85 -90% of cancers  ... 
doi:10.3389/fcell.2020.00717 pmid:32850836 pmcid:PMC7419626 fatcat:go26ygfg2vgw3mv7qoasylv3vy

Genomic and Epigenomic Alterations in Chronic Lymphocytic Leukemia

Ferran Nadeu, Ander Diaz-Navarro, Julio Delgado, Xose S. Puente, Elías Campo
2020 Annual Review of Pathology  
These global studies are revealing the molecular complexity of chronic lymphocytic leukemia and provide new perspectives that have helped to understand its pathogenic mechanisms and improve the clinical  ...  All of these alterations are differentially distributed in clinical and biological subsets of the disease, indicating that they may underlie the heterogeneous evolution of the disease.  ...  ACKNOWLEDGMENTS We thank Silvia Beà, Dolors Colomer, Jose Ignacio Martín-Subero, and Armando Lopez-Guillermo (Hospital Clinic of Barcelona and IDIBAPS) for their helpful comments on the manuscript.  ... 
doi:10.1146/annurev-pathmechdis-012419-032810 pmid:31977296 fatcat:7vkbr7btnnh67eaaz2tllqjhbe

Germline Risk Contribution to Genomic Instability in Multiple Myeloma

Siegfried Janz, Fenghuang Zhan, Fumou Sun, Yan Cheng, Michael Pisano, Ye Yang, Hartmut Goldschmidt, Parameswaran Hari
2019 Frontiers in Genetics  
Genomic instability, a well-established hallmark of human cancer, is also a driving force in the natural history of multiple myeloma (MM) - a difficult to treat and in most cases fatal neoplasm of immunoglobulin  ...  genome and somatic changes in myeloma, and the need to elucidate genetic modifiers in the TME.  ...  AUTHOR CONTRIBUTIONS All authors wrote the manuscript, designed the tables and figures, and read and approved the final version of the review.  ... 
doi:10.3389/fgene.2019.00424 pmid:31139207 pmcid:PMC6518313 fatcat:w7unajf3gfh2tkwystj35lgdy4

RNA Processing and Ribosome Biogenesis in Bone Marrow Failure Disorders

2017 RNA & DISEASE  
This review aims to highlight some of normal processes of RNA metabolism that have been recently demonstrated to be altered in BMFDs.  ...  Bone marrow failure disorders (BMFDs), which are characterized by an early pro-apoptotic phase which results in faulty hematopoiesis and anemia, more often than not progress to outright acute myelogenous  ...  SF3B1 mutations are generally more prevalent in low-risk MDS and have been shown to be independent predictors of favorable clinical outcome in MDS [46] .  ... 
doi:10.14800/rd.1531 fatcat:ejmo52qkwngsjcmjbgvvcp5r64

Cutaneous Melanoma Classification: The Importance of High-Throughput Genomic Technologies

Cristian Scatena, Daniela Murtas, Sara Tomei
2021 Frontiers in Oncology  
The translation of this knowledge and all actual advancements into the clinical practice will be helpful in better defining the different molecular subsets of melanoma patients and provide new tools to  ...  In the recent years, the discovery of driving mutations in melanoma has led to better treatment approaches. The last decade has seen a genomic revolution in the field of cancer.  ...  In a later phase, the ICGC launched the Pan Cancer Analysis of Whole Genomes (PCAWG), also known as the Pan-Cancer Project.  ... 
doi:10.3389/fonc.2021.635488 pmid:34123788 pmcid:PMC8193952 fatcat:eavau2bzyjenjolihyrk6roycu
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