Genomic instability and cancer: an introduction
Open accessAbstract
Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis. During a cell division, genomic instability is minimized by four major mechanisms: high-fidelity DNA replication in S-phase, precise chromosome segregation in mitosis, error free repair of sporadic DNA damage, and a coordinated cell cycle progression. This introduction summarizes the major molecular processes that contribute to these mechanisms in the context of prevention of genomic instability and tumorigenesis.
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Due to the instability of the genome of cancer cells, they have evolved many mechanisms to escape CRISPR/Cas9-mediated genome editing, such as mutation of the PAM sequence and the recognition site.
“Additionally, due to the instability of the genome of cancer cells, they have evolved many mechanisms to escape CRISPR/Cas9-mediated genome editing, such as mutation of the PAM sequence and the recognition site etc. [120–122].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [121]
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“Furthermore, it is undisputed that chronic inflammation may have detrimental effects on DNA integrity and stability, and that genomic instability—a dynamic state characterised by elevated rates of genetic changes resulting from either cellcycle dysfunctionalities or events affecting DNA integrity— is an enabling chara…”
BackgroundDownregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma
Salahshourifar, I., Vincent–Chong, V. K., Chang, H., Ser, H., Ramanathan, A., Kallarakkal, T. G., Rahman, Z. A. A., Ismail, S. M., Prepageran, N., Mustafa, W. M. W., et al. (2015) · Clinical Oral Investigations · doi:10.1007/s00784-015-1467-7 · Cited by 24 · see citing works
“Genomic instability as the hallmark of cancer refers to increased tendency of alteration such as copy number changes, MSI/LOH, single gene mutations, and epigenetic changes in the genome [26].”
BackgroundHara, D., Umehara, Y., Son, A., et al. (2018) · ChemBioChem · doi:10.1002/cbic.201700685 · Cited by 25 · see citing works
Keep Calm and Carry on with Extra Centrosomes
Kalkan, B. M., Özcan, S. C., Quintyne, N. J., Reed, S. L., & Açılan, C. (2022) · Cancers · doi:10.3390/cancers14020442 · Cited by 24 · see citing works
Interaction between APC and Fen1 during breast carcinogenesis
Narayan, S., Jaiswal, A. S., Law, B. K., Kamal, M. A., Sharma, A. K., & Hromas, R. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.04.003 · Cited by 24 · see citing works
“It has been suggested that the increased expression of Fen1 in breast and lung cancer cells may reflect the increased proliferation rate of cancer cells as compared to normal cells or that the increased Fen1 expression may be a response caused by increased DNA damage in cancer cells compared to normal cells [90, 96, 1…”
BackgroundWu, H., Zhang, Z., Zhang, Z., et al. (2021) · Bioengineered · doi:10.1080/21655979.2021.1924555 · Cited by 24 · see citing works
Teng, Y. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i1.300 · Cited by 23 · see citing works
Roles of BCCIP deficiency in mammary tumorigenesis
Droz-Rosario, R., Lu, H., Liu, J., Liu, N.-A., Ganesan, S., Xia, B., Haffty, B. G., & Shen, Z. (2017) · Breast Cancer Research · doi:10.1186/s13058-017-0907-5 · Cited by 22 · see citing works
“Genomic instability can be provoked by inaccurate repair of DNA damage, unfaithful duplication of DNA, and imprecise segregation of mitotic chromosomes [3].”
BackgroundSelf-citationCorrupting the DNA damage response: a critical role for Rad52 in tumor cell survival
Lieberman, R., & You, M. (2017) · Aging · doi:10.18632/aging.101263 · Cited by 21 · see citing works
“Genomic instability signifies an increased tendency of a cell to acquire alterations in the genome during its life cycle [9].”
Persistent genomic instability in peripheral blood lymphocytes from hodgkin lymphoma survivors
Salas‐Labadía, C., Niembro, A., Lozano, V., et al. (2012) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21691 · Cited by 21 · see citing works
“…genomic stability: (a) high-fidelity of DNA replication in S-phase, (b) accurate distribution of chromosomes among daughter cells during mitosis, (c) error-free repair of DNA damage throughout the cell cycle, and (d) cell cycle progression and checkpoint con- trol [Wright, 1999; Shen, 2011].”
BackgroundZsigrai, S., Kalmár, A., Nagy, Z. B., Barták, B. K., Valcz, G., Szigeti, K. A., Galamb, O., Dankó, T., Sebestyén, A. R., Barna, G., et al. (2020) · Cells · doi:10.3390/cells9081864 · Cited by 21 · see citing works
“It is believed that in the case of CRC, tumor initiation and progression are the results of acquired genetic and epigenetic alterations during a series of cell divisions [2,3].”
BackgroundLoss of CCDC6 Affects Cell Cycle through Impaired Intra-S-Phase Checkpoint Control
Thanasopoulou, A., Stravopodis, D. J., DIMAS, K. S., Schwaller, J., & Anastasiadou, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031007 · Cited by 19 · see citing works
“Taken together, our work suggests that loss of CCDC6 results in S phase deregulation that impairs the ability of the cell to maintain genomic integrity and creates a prosperous ground for genomic instability [30,41–43].”
BackgroundMoringa oleifera: A Review on the Antiproliferative Potential in Breast Cancer Cells
Moremane, M. M., Abrahams, B., & Tiloke, C. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45080434 · Cited by 19 · see citing works
“Cancer is described as a disease state in which there is anomalous cell development and uncontrollable cell division [27].”
BackgroundSantibáñez-Andrade, M., Sánchez-Pérez, Y., Chirino, Y. I., et al. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.06.232 · Cited by 19 · see citing works
Angelis, P. M. D., Schjølberg, A. R., Hughes, J. B., et al. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx071 · Cited by 18 · see citing works
Mohamed, H. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2018.12.012 · Cited by 17 · see citing works
Micro-Scale Genomic DNA Copy Number Aberrations as Another Means of Mutagenesis in Breast Cancer
Chao, H., He, X., Parker, J. S., Wei, Z., & Perou, C. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051719 · Cited by 18 · see citing works
“A hallmark of many human cancers is genomic instability, and cancer itself can be thought of as the result of an altered ploidy [1].”
BackgroundSuboptimal extracellular pH values alter DNA damage response to induced double‐strand breaks
Massonneau, J., Ouellet, C., Lucien, F., Dubois, C. M., Tyler, J. K., & Boissonneault, G. (2018) · FEBS Open Bio · doi:10.1002/2211-5463.12384 · Cited by 17 · see citing works
Revisiting the roles of VHR/DUSP3 phosphatase in human diseases
Russo, L. C., Farias, J. O., Ferruzo, P. Y. M., et al. (2018) · Clinics · doi:10.6061/clinics/2018/e466s · Cited by 18 · see citing works
“These alterations or instabilities are minimized by four major mechanisms: high-fidelity DNA replication during S phase, precise chromosome segregation in M phase, accurate and error-free repair of DNA damage, and a cell cycle progression that is coordinated by cell cycle checkpoints (48).”
BackgroundChromosomal Instability as Enabling Feature and Central Hallmark of Breast Cancer
Castellanos, G., Valbuena, D. S., Pérez, E., Villegas, V. E., & Rondón‐Lagos, M. (2023) · Breast Cancer Targets and Therapy · doi:10.2147/bctt.s383759 · Cited by 18 · see citing works
“It is a major driving force for heterogeneity and tumorigenesis.(18,19) Genomic instability leads an accumulation of genetic alterations, which allow tumor cells to acquire proliferative and survival advantages.”
BackgroundExtracellular vesicles in the treatment and diagnosis of breast cancer: a status update
Zhang, X., Wang, C., Yu, J., Bu, J., Ai, F., Wang, Y., Lin, J., & Zhu, X. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1202493 · Cited by 17 · see citing works
NBN and XRCC3 genetic variants in childhood acute lymphoblastic leukaemia
Smolková, B., Dušinská, M., & Hemminki, K. (2014) · Cancer Epidemiology · doi:10.1016/j.canep.2014.08.002 · Cited by 17 · see citing works
“Genome instability is a hallmark of most human cancers [1] including acute lymphoblastic leukaemia (ALL) [2].”
BackgroundRecurrent gene mutations detected in canine mast cell tumours by next generation sequencing
Vozdová, M., Kubı́čková, S., Pál, K., Fröhlich, J., Fictum, P., & Rubeš, J. (2020) · Veterinary and Comparative Oncology · doi:10.1111/vco.12572 · Cited by 17 · see citing works
- Authors
- Shen, Z.
- Affiliations
- Rutgers Cancer Institute (US)
- Corresponding author
- Shen, Z.
- ORCID
- Shen, Z.
- Venue
- Journal of Molecular Cell Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-01-30
- Volume
- 3
- Issue
- 1
- Pages
- 1-3
- ISSN
- 1674-2788 (ISSN-L)
- OpenAlex
- W2043251251
- Cited by
- 229
- References
- 0
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 12 · 2022: 26 · 2021: 18 · 2020: 21 · 2019: 10 · 2018: 13 · 2017: 18 · 2016: 23 · 2015: 12 · 2014: 7 · 2013: 16 · 2012: 10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Cancer Institute (R01CA156706)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- genomic instability, carcinogenesis, DNA replication fidelity, chromosome segregation, DNA repair, cell cycle regulation, cancer prevention
- MeSH terms
- Animals, Cell Division, DNA Replication, Humans, Mitosis, Neoplasms, S Phase, Chromosome Segregation, Genomic Instability
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